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Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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production has been shown to be critical
for host defense against Chlamydia trachomatis infection
in both human and animal studies. Using gene-targeted B cell-deficient
mice, we examined the role of B cells in protective immunity to
C. trachomatis (mouse pneumonitis) (MoPn) lung
infection. B cell-deficient mice were observed to have a significantly
higher mortality rate and in vivo chlamydial growth than did wild-type
mice following MoPn lung infection. Interestingly, B cell-deficient
mice not only lacked Ab responses but also failed to mount an efficient
delayed-type hypersensitivity response following chlamydial lung
infection. In contrast to results obtained from MoPn-infected wild-type
C57BL/6 mice, spleen cells from infected B cell-deficient mice failed
to produce Th1-related (IFN-) or Th2-related (IL-6 and IL-10)
cytokines after Chlamydia-specific in vitro
restimulation. Moreover, unlike wild-type mice, B cell-deficient mice
were not immune to rechallenge infection following recovery from
primary chlamydial infection. The data indicate that B cells play an
important role in host defense to primary and secondary chlamydial
infection and suggest that B cells are crucial for the initiation of
early T cell responses to chlamydial infection. This study provides
evidence for the role of B cells in the in vivo priming of T cells
during infection with the intracellular bacterial pathogen, C.
trachomatis. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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production) (8, 9, 10). Moreover, using a murine
model of chlamydial lung infection, we previously reported that strong
cell-mediated immune response (delayed-type hypersensitivity
(DTH)3) and IFN-
production were associated with more rapid clearance of the mouse
pneumonitis (MoPn) from the lung (11). Using the same model, we also
demonstrated that 
ß TCR, but not 
TCR, T cells play the
dominant role in host defense against chlamydial infection (12).
Although chlamydia elicits strong local and systemic Ab responses in
both humans and animals, the role that such Abs play in protective
immunity to chlamydial infection is uncertain (13, 14, 15). Notably, a
series of studies conducted over a decade ago showed that B
cell-deficient mice generated by chronic treatment with anti-µ
Abs were able to resolve primary and secondary MoPn infection as
readily as normal mice following genital and respiratory challenge
infections, suggesting that B cells are not essential for host defense
against chlamydial infection (16, 17). Since chronic anti-µ Ab treatment involves in vivo delivery of an extraordinary amount of Ab, it may alter the microenvironment and concomitant cell-to-cell interactions that occur during chlamydial infection. As well, in spite of the large amount of Ab used, anti-µ Ab treatment may not completely deplete B cell populations in vivo, and although serum IgM is reduced to undetectable levels, IgG is generally readily detectable, albeit at levels 10- to 1000-fold lower than normal (18). Therefore, additional studies using alternative approaches to deplete B lymphocytes are needed to elucidate whether B cells play a role in host defense against chlamydial infection. Accordingly, we used B cell-deficient mice (µMT) generated by disruption of the transmembrane portion of the µ-chain gene (19) to reexamine the role played by B cells in the resolution of primary and resistance to secondary MoPn lung infection. In striking contrast to previous reports regarding chlamydial infection in anti-µ Ab-treated mice, gene knockout B cell-deficient (µMT) mice showed dramatically increased mortality and in vivo chlamydial growth following MoPn lung infection. B cell-deficient (µMT) mice showed complete absence of Ab responses and greatly impaired cell-mediated immune responses (DTH) to chlamydial elementary bodies (EBs). Most strikingly, spleen cells obtained from MoPn-infected µMT mice failed to produce T cell-derived cytokines after in vitro EB restimulation. The results argue that B cells play an essential role in host defense to chlamydial lung infection and suggest that B cells are crucial for the initiation of T cell responses during chlamydial infection. The study provides further evidence that B cells are necessary for T cell priming in vivo following infection with the intracellular pathogen, C. trachomatis.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Female B cell-deficient (µMT) mice with a C57BL/6 genetic background (C57BL/6-Igh-6>tm1Cgn) were purchased from The Jackson Laboratory (Bar Harbor, ME). Age- and sex-matched wild-type C57BL/6 mice were purchased from The Jackson Laboratory or Charles River Canada (St. Constant, Quebec, Canada). All the animals were maintained under specific pathogen-free conditions in the central animal facilities of the University of Manitoba. Mice 8 to 14 wk of age were used for the study.
Mouse pneumonitis
The mouse pneumonitis biovar (Nigg strain) of C. trachomatis (MoPn) was grown in HeLa 229 cells and purified by discontinuous density gradient centrifugation. Infectivity of the purified EBs was titrated by infection of HeLa cell monolayers followed by methanol fixation of cells and enumeration of inclusions which were stained by a genus-specific mAb and horseradish peroxidase conjugate. The procedure of MoPn purification and infectivity determination was the same as previously described (11).
Infection
Mice were inoculated intranasally with various doses of MoPn in a volume of 40 µl. The mice were monitored daily for viability and weight changes following infection. As defined for individual experiments, mice were killed at selected days after infection, and lungs were aseptically isolated and homogenized in sucrose-phosphate-glutamic acid (SPG) buffer. Tissue homogenates were spun at 500 x g for 10 min at 4°C, and supernatants were kept at -70°C until tested.
Antibody measurement
Serum IgM, IgG1, IgG2a, and IgA Abs to MoPn EBs in each individual mouse were determined by ELISA as described (11). Results are expressed as ELISA titers at 60 min using the endpoint (cutoff at OD405 0.5) of the titration curves compared with an internal standard (sera from C57BL/6 mice repeatedly infected with MoPn) run in each assay. Sera from naive C57BL/6 mice showed titers < 100 for IgM and < 50 for all other isotypes in this testing system. All serum samples were measured at least twice.
Determination of DTH responses
MoPn-specific DTH was measured as described (11). Mice were injected in the hind footpad with 25 µl of heat-inactivated MoPn EBs (5 x 104 inclusion-forming units (IFUs)) in one side and the same volume of SPG buffer in the other side. The difference in thickness between the two footpads at 48 and 72 h was used as a measure of the DTH response. No measurable difference was found between the two footpads in uninfected control mice.
Cytokine analysis of splenocytes
Spleen cell cytokine production was analyzed as described
(11, 20). Mice were killed at various days following infection and
spleen cells were cultured at 7.5 x 106 cells/ml with
heat-inactivated MoPn EBs (1 x 105 IFU/ml) in the
presence or absence of anti-CD4 (YTS-191) mAb (kindly provided by
Dr. K. T. HayGlass, University of Manitoba, Winnepeg, Canada) at 5
µg/ml. Culture supernatants were collected at 72 and 96 h for
cytokine determination. All cytokine determinations were done by ELISA
as previously described (11). Purified capture and biotinylated
detection Abs were purchased from PharMingen (San Diego, CA). IFN-
levels in 72-h culture supernatants were tested by a two-mAb sandwich
ELISA (XMG1.2 for capture and R4-6A2 for detection). IL-6 and IL-10
were tested using 96-h culture supernatants. IL-6 assays used MP5-20F3
as capture and mAb MP5-32C11 as detector Abs, respectively. IL-10
assays used JES-2A5 and SXC-1 as capture and detection Abs. Recombinant
cytokine proteins (PharMingen) were used as standards in all the
assays.
Statistics
Difference in mortality between wild-type and B
cell-deficient mice were analyzed by the 
2 test. Body
weight loss and cytokine production were analyzed by Students’
t test. IFUs of MoPn in the infected lungs were transformed
to base 10 logarithms and analyzed by Students’ t
test.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Wild-type and B cell-deficient mice were intranasally inoculated
with 1 x 104 IFU of MoPn, and the viability of the
mice was monitored daily until 30 days postinfection. As shown in
Figure 1
A, B cell-deficient
mice showed early death starting at day 11 postinfection. Up to 30 days
postinfection, most wild-type mice were still alive (the mortality rate
was 19%), while 66% of the B cell-deficient mice had died. The
difference in mortality between B cell-deficient and wild-type mice was
statistically significant (p = 0.0003). Similar
results were obtained when mice were infected with a lower dose of MoPn
(4 x 103 IFU, Fig. 1B); the difference
between wild-type and B cell-deficient mice in mortality was again
statistically significant (p = 0.004). When the
severity of infection was analyzed based on body weight loss, B
cell-deficient mice showed earlier and greater body weight loss than
wild-type mice. Since B cell-deficient mice started to die from day 11
(Fig. 1A) or day 12 (Fig. 1B) postinfection in
the two separate experiments, the body weight changes shown in Figure 2 compare only the differences between
wild-type and B cell-deficient mice in the period before any mouse
death had occurred in the two experiments (days 11 and 12,
respectively).
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shows four separate
experiments in which mice were infected intranasally with 1 x
103 IFUs of MoPn and were killed at various days
postinfection. B cell-deficient mice showed higher (10–1000-fold) in
vivo growth of MoPn than did wild-type mice in all experiments testing
chlamydial in vivo growth at days 7, 10, 15, and 17 postinfection. The
differences were statistically significant in the one large experiment
(8–9 mice/group) at day 17 postinfection (p =
0.0007). In aggregate, the data indicate that B cell-deficient mice are
more susceptible to MoPn infection than wild-type mice as demonstrated
by higher mortality rate, greater morbidity rate, and delayed clearance
of MoPn infection from the lung.
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We previously demonstrated that the DTH response to C.
trachomatis is highly correlated with more rapid clearance of the
organism in vivo and that the DTH response to C. trachomatis
infection is entirely dependent on ß T lymphocytes (11, 12). Since
B cell-deficient mice showed considerably higher mortality and in vivo
chlamydial growth (Fig. 1
; Table I) we analyzed DTH responses in the B
cell-deficient mice in comparison with wild-type control mice. Mice
were intranasally infected with 1 x 103 IFUs of MoPn
and Chlamydia-specific DTH responses were tested at day 13
postinfection. As shown in Figure 3, B
cell-deficient mice showed significantly reduced DTH responses to MoPn
than did wild-type mice (p = 0.009 at 48
h, and p = 0.047 at 72 h). Not surprisingly, Ab
responses were completely abolished in µMT mice, confirming the B
cell deficiency of these mice (Table II).
Overall, the data show that B cells are necessary not only for
producing Ab to Chlamydia but also for the initiation of
efficient T cell responses (DTH) to pulmonary chlamydial infection.
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A consistent body of evidence demonstrates that Th1-like T
cell responses and IFN- production are critical for clearance of
C. trachomatis infection (11, 20, 21, 22) and that
cytokine patterns of spleen cells are tightly associated with host
susceptibility or resistance to chlamydial lung infection (11). The
failure of B cell-deficient mice to mount efficient DTH responses
suggests that T cell function in these mice is impaired or altered. To
more directly examine T cell responses and cytokine production in B
cell-deficient mice and their relationship with susceptibility to
chlamydial infection, we analyzed the Ag-specific cytokine production
of spleen cells in µMT mice following MoPn infection. As shown in
Table III, splenocytes from infected B
cell-deficient mice completely or partially failed to produce either
Th1-related (IFN-) or Th2-related (IL-6 and IL-10) cytokines after
in vitro Chlamydia-specific restimulation. Cytokine
production, including IFN-, IL-6, and IL-10, in MoPn-infected
wild-type mice was completely or largely dependent on CD4 T cells
because anti-CD4 mAb (YTS-191) blocked the production of these
cytokines (Ref. 12, Table III) while anti-CD8 mAb (YTS-169) failed
to do so (data not shown). To examine whether the impairment of T cell
response in µMT mice following MoPn infection is due to an intrinsic
deficiency of T cells, we analyzed spleen T cell function in naive
µMT mice by testing its proliferative response and IFN- production
following polyclonal T cell (Con A) stimulation. As shown in Table IV, spleen cells from µMT mice respond
normally to Con A stimulation in terms of proliferation and cytokine
production, suggesting that T cells were intact in µMT mice. In
aggregate, the data show that the failure of B cell-deficient mice to
generate efficient cell-mediated immune responses (DTH) to chlamydial
infection is associated with the impaired cytokine, including IFN-,
production by CD4 T cells following chlamydial infection.
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production) in vitro after organism-specific restimulation. As shown in
Table V, addition of naive B cells to the
spleen cell culture of MoPn-infected µMT mice did not generate
IFN- production in the presence of heat-inactivated MoPn
stimulation. Similarly, addition of purified naive B cells to the
culture of CD4-enriched spleen cells collected from MoPn-infected
wild-type mice failed to significantly increase Ag-specific production
of IFN- (Table V). The results suggest that the initial in vivo
interaction between T cells and B cells is critical for T cell priming
during chlamydial infection. Nevertheless, the mechanisms underlining
this T-B cell interaction were not defined by the in vitro experiments.
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As shown in Figure 1, about one-third of the B
cell-deficient mice and >80% of wild-type mice survived primary
infection. These mice recovered their original body weights within 1
month of the infection, suggesting the resolution of the primary
infection. Previous studies showed that C57BL/6 mice completely clear
lung infection within 1 month (11). To examine whether primary
infection resulted in immunity, we reinfected the survivors of
primarily infected B cell-deficient and wild-type mice with a
relatively large dose of MoPn (1 x 104 IFU) 47 to 50
days following primary infection. As controls, naive B cell-deficient
and wild-type mice that were age-matched with the recovered mice were
also infected in the same experiment. As shown in Figure 4, the primed wild-type survivors were
immune to secondary infection as shown by negligible weight loss and
100% survival rate at 15 days following secondary infection. However,
B cell-deficient mice that had recovered from previous chlamydial
infection showed remarkably greater body weight loss and mortality
(50%) over the same time period than primed wild-type survivors. The
magnitude of body weight loss among primed B cell-deficient mice
following challenge infection was similar to that of B cell-deficient
mice that were infected for the first time, and the mortalities in
these two groups were not statistically different
(p = 0.24) (Fig. 4). The data demonstrate that
B cell-deficient mice, unlike wild-type mice, do not develop acquired
immunity to challenge infection and suggest that B cells are critical
in host defense not only for primary infection but also for resistance
to secondary chlamydial infection.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The most evident function of B cells in immune response is the production of Abs to specific Ags. C. trachomatis has numerous Ags, including the major outer membrane protein, which are highly immunogenic in inducing Ab responses (14). Although Ab responses have been extensively studied, their role in protection against in vivo chlamydial infection remains unclear (13, 14, 15, 23, 24, 25, 26, 27, 28, 29). In vitro studies have clearly shown that Abs to specific chlamydial Ags such as the major outer membrane protein can neutralize chlamydial infectivity in cultured cell lines (23, 24). Some in vivo studies, including direct delivery of anti-chlamydial Abs and the hybridoma backpack model, also demonstrated measurable degrees of protection (25, 26, 27). However, serum Ab, especially IgG, responses have been poorly correlated with clearance of chlamydial infection in both animal models of infection (11, 15) and epidemiologic studies of affected humans (13, 14, 29). Nevertheless, none of these studies has answered the question as to whether B cells are essential in host defense against chlamydial infection. The data reported in the present study unambiguously demonstrate that gene knockout B cell-deficient mice have a serious defect in resistance to primary and secondary chlamydial lung infection and show that B cells are essential for host defense against C. trachomatis infection.
The necessity for B cells, however, may not simply mean the
requirement for Abs for protective immunity to chlamydial infection. An
interesting and probably more important observation from this study is
the impairment of T cell responses to chlamydial Ags that is detected
in B cell-deficient mice. The impairment of T cell responses is not due
to intrinsic deficiency of T cells in B cell-deficient mice because the
cells showed normal levels of proliferation and cytokine production to
polyclonal (Con A) stimulation (Table IV). This finding of defective T
cell response to chlamydial Ag in gene knockout B cell-deficient mice
suggests that B cells play a crucial role in the initial phase of T
cell activation following chlamydial infection. It has long been
documented that B cells can function as APCs in initiation of T cell
responses (29, 30, 31, 32). B cells that express Abs specific for an Ag are
highly efficient for the presentation of that Ag to T cells, and the
binding of Ag with its Ag receptor on B cells signals biologic changes
in the class II presentation pathway of B cells (33). However, it is
still debatable whether B cells are able to, or are essential for,
priming of T cell responses in vivo. The available data are
inconclusive with some studies showing failure of T cell responses and
others showing normal T cell responses in B cell-deficient mice
(31, 32, 33, 34, 35, 36, 37, 38, 39). This inconsistency may reflect differences in Ags tested and
model systems used. Notably, reports of T cell function in gene
knockout B cell-deficient mice have shown normal T cell responses to
soluble protein Ags (36, 37). Unlike the protein Ags, however,
chlamydia EBs express LPS and other non-LPS molecules in their outer
membrane that are mitogenic for B lymphocytes (40, 41). More
importantly, we have found that gene knockout mice deficient in T cells
(ß and TCR) produce significant levels of IgM Ab following
MoPn infection, which indicates the direct activation of B lymphocytes
by chlamydia EBs (X. Yang and R. C. Brunham, unpublished data). It
has been demonstrated that LPS-activated B cell blasts, but not resting
B cells, can function as efficient APCs for T cell priming (39). The B
cell-stimulating characteristics of C. trachomatis imply
that the organism may activate B cells in vivo on initial entry in the
host, possibly enabling its Ags to be presented by activated B cell
lymphoblasts. The observation we have made with C.
trachomatis are not without precedent. It was recently reported
that B cell-deficient mice showed increased in vivo growth of another
intracellular bacterial pathogen, Mycobacterium
tuberculosis, and exhibited diminished in vitro T
cell-proliferative responses to mycobacterial Ag (42). We hypothesize
that the ability of a pathogen or Ag to activate B cells early in an
adaptive immune response may determine whether B cells play a role in
the Ag presentation to and/or costimulation of T cells.
While this article was in preparation, Su et al. (43) reported that gene-disrupted B cell-deficient mice mounted normal levels of DTH response and cleared primary infection as efficiently as wild-type mice following genital MoPn infection. The reason for the differences between their findings and our data is not clear. However, the differences may be more apparent than real since the two approaches differed in several respects. First, the studies differ in the chlamydial infection model used. We used a pulmonary infection model, and infection at this site appears to be a more sensitive test of immunity to chlamydial infection than does a genital infection model, possibly because MoPn lung infection induces more severe diseases. Such differences between lung and genital MoPn model infections were also observed when class I-deficient mice were evaluated (reviewed by Yang and Brunham (2)). Secondly, the times at which T cell responses were measured differ in the two studies. Su et al. (43) measured DTH and cytokine production after complete resolution of chlamydial infection (day 30 postinfection), while our study measured T cell responses in the early (days 7 and 10) and intermediate (day 17) phases of immune mediated clearance. Theoretically, measurement of T cell and cytokine responses during the process of infection should be more representative of the pattern of immune responses to chlamydial infection. In aggregate, the data from the two studies may suggest that B cell-deficient mice have delayed but not absent T cell responses. Such kinetic differences were also observed in lymphocytic choriomeningitis virus-infected B cell-deficient mice (44). Since high dose lung MoPn infection is lethal for B cell-deficient mice, such mice may not have sufficient time to generate and amplify efficient T cell responses through Ag presentation by non-B cell APCs. In contrast, chlamydial genital infection is relatively minor and B cell-deficient mice clearly survive. Therefore, T cell responses can reach normal level during the later stages in genital infection model via activation by other APCs. In line with this hypothesis, B cell-deficient mice in our infection model system showed reduced but still measurable DTH responses, indicating that the B cell is not the only cell type capable of presenting chlamydial Ags to T cells. Finally, unlike the lung infection model, the chlamydial genital infection model requires the administration of medroxyprogesterone to enhance infection. How sex steroids influence the immune response to chlamydial infection is uncertain. However, recent studies have shown that progesterone favors the development of Th2-like responses and is suppressive for Th1-like responses (45, 46, 47, 48, 49). It is possible, therefore, that Th1-like responses such as DTH in the mice with genital chlamydial infection is lower than that in the mice with lung infection because progesterone was used for establishing genital infection. Consequently, in the genital infection model, the difference in DTH response between wild-type and µMT mice may not as obvious as that in the lung infection model. Clearly, more study is necessary to clearly elucidate the mechanisms underlining the surprising differences in B cell requirements for host defense during genital and lung chlamydial infection.
Since the two arms (humoral and cell-mediated) of immune responses are either completely or partially impaired in B cell-deficient mice, this study does not provide conclusive information regarding the relative importance of each effector mechanism in host defense against chlamydial infection. Rather, this study demonstrates the involvement of and the critical role for B cells in protective immunity to chlamydial infection. Moreover, the finding that B cells function in the initiation of T cell responses suggests that further efforts should focus on the role of B cells in the priming of T cells and their potential importance in host defense to infection with intracellular bacterial pathogens in general.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Xi Yang, Department of Medical Microbiology, University of Manitoba, Room 525, 730 William Avenue, Winnipeg, Manitoba, Canada R3E OW3. E-mail address:
3 Abbreviations used in this paper: DTH, delayed-type hypersensitivity; MoPn, mouse pneumonitis; EBs, elementary bodies; IFUs, inclusion-forming units.
Received for publication July 9, 1997. Accepted for publication April 7, 1998.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection. J. Immunol. 156:4338.[Abstract]
/ß and / T cell in acquired immunity to Chlamydia
trachomatis mouse pneumonitis pulmonary infection.
Immunology. In press.
and TNF and reduced IL-10 production by placental cells. J. Immunol. 156:653.[Abstract]
response and increased production of T helper 2 cytokines. J. Immunol. 156:644.[Abstract]
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A. E. Matthews, S. R. Weiss, M. J. Shlomchik, L. G. Hannum, J. L. Gombold, and Y. Paterson Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver J. Immunol., November 1, 2001; 167(9): 5254 - 5263. [Abstract] [Full Text] [PDF]
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S. G. Morrison and R. P. Morrison Resolution of Secondary Chlamydia trachomatis Genital Tract Infection in Immune Mice with Depletion of Both CD4+ and CD8+ T cells Infect. Immun., April 1, 2001; 69(4): 2643 - 2649. [Abstract] [Full Text] [PDF]
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 P. P.L. Chiu, D. V. Serreze, and J. S. Danska Development and Function of Diabetogenic T-cells in B-cell-Deficient Nonobese Diabetic Mice Diabetes, April 1, 2001; 50(4): 763 - 770. [Abstract] [Full Text]
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J. U. Igietseme, J. L. Portis, and L. L. Perry Inflammation and Clearance of Chlamydia trachomatis in Enteric and Nonenteric Mucosae Infect. Immun., March 1, 2001; 69(3): 1832 - 1840. [Abstract] [Full Text] [PDF]
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C. M. Bosio and K. L. Elkins Susceptibility to Secondary Francisella tularensis Live Vaccine Strain Infection in B-Cell-Deficient Mice Is Associated with Neutrophilia but Not with Defects in Specific T-Cell-Mediated Immunity Infect. Immun., January 1, 2001; 69(1): 194 - 203. [Abstract] [Full Text] [PDF]
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S. G. Morrison, H. Su, H. D. Caldwell, and R. P. Morrison Immunity to Murine Chlamydia trachomatis Genital Tract Reinfection Involves B Cells and CD4+ T Cells but Not CD8+ T Cells Infect. Immun., December 1, 2000; 68(12): 6979 - 6987. [Abstract] [Full Text] [PDF]
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C. M. Bosio, D. Gardner, and K. L. Elkins Infection of B Cell-Deficient Mice with CDC 1551, a Clinical Isolate of Mycobacterium tuberculosis: Delay in Dissemination and Development of Lung Pathology J. Immunol., June 15, 2000; 164(12): 6417 - 6425. [Abstract] [Full Text] [PDF]
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S. C. Smelt, S. E. J. Cotterell, C. R. Engwerda, and P. M. Kaye B Cell-Deficient Mice Are Highly Resistant to Leishmania donovani Infection, but Develop Neutrophil-Mediated Tissue Pathology J. Immunol., April 1, 2000; 164(7): 3681 - 3688. [Abstract] [Full Text] [PDF]
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H. Kang, J. S. Remington, and Y. Suzuki Decreased Resistance of B Cell-Deficient Mice to Infection with Toxoplasma gondii Despite Unimpaired Expression of IFN-{gamma}, TNF-{alpha}, and Inducible Nitric Oxide Synthase J. Immunol., March 1, 2000; 164(5): 2629 - 2634. [Abstract] [Full Text] [PDF]
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H.-W. Mittrucker, B. Raupach, A. Kohler, and S. H. E. Kaufmann Cutting Edge: Role of B Lymphocytes in Protective Immunity Against Salmonella typhimurium Infection J. Immunol., February 15, 2000; 164(4): 1648 - 1652. [Abstract] [Full Text] [PDF]
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P. Mastroeni, C. Simmons, R. Fowler, C. E. Hormaeche, and G. Dougan Igh-6-/- (B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses to Salmonella Antigens Infect. Immun., January 1, 2000; 68(1): 46 - 53. [Abstract] [Full Text] [PDF]
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K. L. Elkins, C. M. Bosio, and T. R. Rhinehart-Jones Importance of B cells, but Not Specific Antibodies, in Primary and Secondary Protective Immunity to the Intracellular Bacterium Francisella tularensis Live Vaccine Strain Infect. Immun., November 1, 1999; 67(11): 6002 - 6007. [Abstract] [Full Text] [PDF]
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R. Allendorfer, G. D. Brunner, and G. S. Deepe Jr. Complex Requirements for Nascent and Memory Immunity in Pulmonary Histoplasmosis J. Immunol., June 15, 1999; 162(12): 7389 - 7396. [Abstract] [Full Text] [PDF]
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C. P. Wong, C. Y. Okada, and R. Levy TCR Vaccines Against T Cell Lymphoma: QS-21 and IL-12 Adjuvants Induce a Protective CD8+ T Cell Response J. Immunol., February 15, 1999; 162(4): 2251 - 2258. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) mice were intranasally
infected with MoPn and monitored daily for mortality. A,
Mice (16 mice/group for wild-type and 12 mice/group for µMT) were
infected with 1 x 104 IFUs of MoPn; B,
Mice (12 mice/group) were infected with 4 x 103 IFU
of MoPn.
) (8 mice/group) and µMT (
) (9 mice/group) mice were
infected intranasally with 1 x 103 IFUs of MoPn and
delayed-type hypersensitivity (DTH) were determined at 13 days
following infection as described in Materials and
Methods. Footpad swelling at 48 and 72 h was shown
(mean ± SEM).
) and B cell-deficient (
) mice were initially
intranasally infected with 4 x 103 or 1 x
104 IFUs of MoPn as described in Figures 1