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Departments of
*
Microbiology and Immunology and
Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095; and
Emory Vaccine Center & Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The lectin peanut agglutinin
(PNA)3 is known to bind T
cells activated in vitro (11, 12, 13, 14). PNA binds with the highest affinity
to the disaccharide sequence Galß1,3GalNAc, a sequence typically
found in O-linked glycans (15). The Galß1,3GalNAc
disaccharide can be modified by the activity of specific enzymes.
Sialyltransferase enzymes can add sialic acid residues to this
structure to form the tetrasaccharide
SA
2,3Galß1,3(SA2,6)GalNAc, while endogenous neuraminidase
(sialidase) activity can remove these sialic acid residues (16). The
addition of sialic acid to the Galß1,3GalNAc sequence inhibits PNA
binding, presumably by masking the PNA binding site. Murine T cells
activated in vitro show increased PNA binding compared with resting
cells, indicating loss of sialic acid from cell surface
O-glycans during activation (11, 12, 13, 14). Possible mechanisms
responsible for the decrease in sialic acid residues on
O-glycans on activated T cells include decreased sialylation
by sialyltransferases and increased removal of sialic acid by
endogenous neuraminidase (12, 14).
In this study, we have examined the changes in sialic acid residues on T cells during viral infection in vivo using the mouse model of infection with lymphocytic choriomeningitis virus (LCMV). Adult mice infected with LCMV (Armstrong strain) develop an acute infection characterized by a large expansion of activated CD8+ T cells and a potent antiviral CTL response, which mediates viral clearance within 2 wk (17, 18). The mice then develop LCMV-specific memory CD8+ T cells that persist for the life of the animal (19, 20, 21). We show in this study that activation of CD8+ T cells in vivo is accompanied by increased neuraminidase activity and decreased levels of sialic acid on surface glycoproteins. These changes are seen not only after LCMV infection, but also after infection of mice with vaccinia virus and vesicular stomatitis virus (VSV). In addition, we show that virus-specific memory CD8+ T cells remain hyposialylated and can be distinguished from naive CD8+ T cells based on PNA binding.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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C57BL/6J (H-2b) mice (6–10 wk old) used in this study were purchased from The Jackson Laboratory (Bar Harbor, MA). LCMV-immune mice were made by injecting 6- to 12-wk-old C57BL/6J (H-2b) mice with 2 x 105 PFU of LCMV i.p. and were analyzed for memory CD8+ T cells greater than 30 days postinfection.
Virus
The Armstrong CA 1371 strain of LCMV, vaccinia virus, and VSV was used in this study. The mice were infected i.p. with 1 x 106 PFU of LCMV, or with 2 x 106 PFU of VSV, or with 5 x 106 PFU of vaccinia virus.
Staining reagents and flow cytometry
FITC-conjugated anti-mouse CD8 (anti-Lyt-2.2) and phycoerythrin (PE)-conjugated anti-mouse CD4 (anti-L3T4) were purchased from Becton Dickinson (San Jose, CA). Biotin-conjugated PNA was purchased from Boehringer Mannheim (Mannheim, Germany) and used at a concentration of 0.4 mg/106 spleen cells in the presence or absence of 0.2 M galactose as inhibitor of specific lectin binding. PE-streptavidin or FITC-streptavidin was used in conjunction with the biotin-conjugated PNA (Caltag, South San Francisco, CA). FITC-conjugated rat anti-CD44 mAb (activation marker) was purchased from PharMingen (San Diego, CA). Mouse spleen cells were stained as described previously (19, 20).
In vitro depletion of CD8+ T and CD4+ T cells
To deplete CD8+ T cells, spleen cells were incubated with anti-CD8 mAb (anti-Lyt-2.2) purchased in the form of ascites fluid (Cedarlane, Hornby, Ontario, Canada), followed by treatment with low tox M rabbit complement (Cedarlane). To deplete CD4+ cells, spleen cells were treated with rat anti-mouse CD4 mAb (RL172.4) and complement. After depletion, cells were washed, counted, and assayed for neuraminidase activity.
Neuraminidase assay
The endogenous neuraminidase activity of whole spleen cells, CD8+-depleted spleen cell fractions, and CD4+-depleted spleen cell fractions was examined by a fluorometric assay, as described previously (13). Neuraminidase activity was determined by the amount of fluorescent product 4-methylumbelliferone (4-MU) that was cleaved from its substrate 4-methylumbelliferyl-N-acetylneuraminic acid (4-MU-NANA) by neuraminidase. Cells were washed in PBS, resuspended at 108/ml in 10 mM phosphate buffer, 12 mM CaCl2 (pH 6.8), and lysed by quick freezing in a solid CO2/ethanol bath. A total of 50 µl of cell homogenate or 50 µl of 4-MU standard (standards from 0.1 to 25 mM) was added to 25 µl of 80 mM sodium acetate (pH 4.4) and 25 µl of 0.2 mM 4-MU-NANA. A blank consisting of 50 µl CaCl2 in place of cell homogenate was used to determine the nonspecific degradation of the substrate. Samples were incubated at 37°C for 1 h, and the reaction was terminated by the addition of 1 ml of 0.5 M sodium carbonate (pH 10.7). Samples were centrifuged for 10 min at 1300 x g, and the supernatants were collected. Using a spectrofluorometer, the fluorescence was determined with emission wavelength at 440 nm and excitation at 365 nm. A standard curve was made plotting the fluorescence vs the concentration of the 4-MU standards. The concentration of 4-MU produced in each sample was calculated by subtracting the fluorescence of the blank from the fluorescence of the sample and plotting this result on the standard curve. Activity is expressed per 108 spleen cells, and 1 U of activity is defined as the amount of enzyme that releases 1 mM of 4-MU per hour at 37°C. The 4-MU and 4-MU-NANA were purchased from Fluka BioChemika (Buchs, Switzerland).
Purification and sorting of PNAhighCD8+ T cells
Before sorting by flow cytometry, spleen cells from LCMV-immune mice were enriched for CD8+ T cells using the Mouse T Cell Subset Column Kit (R & D Systems, Minneapolis, MN). This enriched CD8+ T cell population was incubated for 1 h with biotin-conjugated PNA at a concentration of 4 mg/107 cells in 1 ml of PBS. Cells were washed twice and stained with FITC-conjugated mouse anti-CD8 mAb (Becton Dickinson) and with streptavidin-PE (Caltag) at concentrations recommended by manufacturer. PNA-labeled cells were gated on CD8+ T cells, and these cells were sterilely sorted into PNAhigh (top 30% fluorescent) and PNAlow (bottom 30%) populations on a FACStarPlus dual cell sorter (Becton Dickinson). There was no crossover between the two sorted fractions, as checked by postsort flow-cytometric analysis of each sorted population. The two populations were used in limiting dilution analysis.
Limiting dilution assay
The LCMV-specific CTL precursor (CTLp) number and frequency in the PNAhigh and PNAlow fractions were quantitated by limiting dilution assay, as described previously (19). The method of Taswell was used to determine LCMV-specific frequency (22).
Intracellular IFN-
stain
Spleen cells were cultured for 5 h in 96-well flat-bottom
plates at a concentration of 1 x 106 cells/well
in 0.2 ml complete medium supplemented with 10 U/well human rIL-2 and 1
µl/ml Brefeldin A (Golgistop; PharMingen) either in the presence
or absence of CD4 or CD8 epitope peptides (1 and 0.1 µg/ml,
respectively). To analyze CD4 responses, peptides NP 309–329 and GP
61–80 were used (23), and for CD8 responses we used NP 396, GP 33, and
GP 276 (24, 25). After 5 h of stimulation, cells were harvested,
washed, and surface stained with Cychrome-conjugated rat anti-mouse
CD8 or CD4 Ab and biotin-PNA, followed by streptavidin-PE. After
washing the unbound Abs, cells were subjected to intracellular cytokine
stain using the Cytofix/Cytoperm kit, according to manufacturer’s
instructions (PharMingen). For intracellular IFN- stain, we used
FITC-conjugated rat anti-mouse IFN- mAb (clone XMG
1.2).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The CD8+CTL activity in the spleens of LCMV-infected mice peaks at approximately day 8 postinfection. At this time, the number of activated CD8+ T cells increases as much as 10-fold. Between day 8 and 15 postinfection, there is a sharp decrease in CTL activity and the number of activated CD8+ T cells. Between day 15 and 30 postinfection, the number of activated CD8+ cells continues to fall, eventually reaching homeostatic levels. LCMV-specific memory CD8+ T cells develop and are maintained at a stable frequency for the life of the mouse (19, 20, 21).
To detect changes in the sialylation state of T cells activated in
vivo, we examined the ability of T cells harvested from the spleens of
LCMV-infected mice at days 0, 5, 8, 15, and 30 postinfection to bind
PNA (Fig. 1
A).
CD8+ T cells from uninfected mice (day 0) showed low levels
of PNA binding (PNAlow). By day 5 postinfection, as the
activated CD8+ T cell population begins to expand in
LCMV-infected mice, there was an increase in the number of
PNAhighCD8+ T cells, and by day 8, the
PNAhigh population had expanded to comprise 29% of the
spleen population. The percentage of
PNAhighCD8+ T cells declined between days 8 and
30, corresponding with the decrease in the number of activated
CD8+ cells after an acute LCMV infection. However, at day
30, a small PNAhigh population appeared to persist when
compared with naive mice (8% of splenocytes from immune mice were
PNAhigh, compared with 1% of splenocytes from naive mice).
Figure 2 shows the total number of
PNAhigh and PNAlowCD8+ T cells per
spleen at various time points (days 5, 8, 15, 30, >60) after LCMV
infection. Notice that at the peak of infection (day 8) there was a
greater than 15-fold increase in the number of
PNAhighCD8+ T cells.
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B, there was a complete correlation with activation
(CD44high) and PNAhigh binding. At 8 days
postinfection, nearly all CD8+ T cells in the spleens of
LCMV-infected mice were CD44high, and all of these cells
showed increased PNA binding. This was in contrast to CD8+
T cells from uninfected mice, in which the majority of the cells were
CD44low and PNAlow. Note that even in normal
mice the population of CD8+ T cells that was
CD44high showed increased binding to PNA. However, the
levels of both CD44 and PNA were lower in this population than that
seen in CD8+ T cells from LCMV-infected mice. Alteration in cell surface carbohydrates on activated CD8+ T cells is a common feature of viral infection
To determine whether the increase in PNA binding on activated
CD8+ T cells was specific to LCMV infection or was a
general phenomenon in viral infections, we examined the pattern of PNA
binding to CD8+ cells in mice acutely infected with
vaccinia virus or VSV. At 8 days postinfection, splenic
CD8+ T cells from virally infected mice were stained with
PNA and anti-CD8 Ab and analyzed by flow cytometry (Fig. 3). Compared with uninfected mice at day
0, the vaccinia virus-infected mice showed a shift in the
CD8+ population from PNAlow to
PNAhigh. This shift was also seen in VSV-infected mice,
although the magnitude of the shift was less than that seen with
vaccinia virus infection. In both cases, as observed in LCMV infection,
there was an increase in PNA binding to CD8+ T cells
activated during viral infection. Thus, increased PNA binding, i.e.,
decreased cell surface sialylation of activated CD8+ T
cells, was not restricted to LCMV infection, but appeared to be a
general phenomenon in viral infections.
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As mentioned previously, PNA binds with high affinity to the
disaccharide Galß1,3GalNAc, which is found on O-linked
oligosaccharides. Sialic acid can be added to this structure, and the
presence of sialic acid masks the PNA binding sites. One mechanism that
could account for the changes in PNA binding involves the removal of
sialic acid by endogenous neuraminidase activity. Higher levels of
neuraminidase activity could increase the number of exposed PNA binding
sites on cell surface glycoproteins. Therefore, we examined whether T
cells from LCMV-infected mice had an increased endogenous neuraminidase
activity. Using a fluorometric assay, we analyzed the endogenous
neuraminidase activity in spleen T cells from uninfected and
LCMV-infected mice. As shown in Figure 4A, total spleen cells from
day 8 LCMV-infected mice had approximately threefold greater
neuraminidase activity than spleen cells from uninfected mice.
Furthermore, the increase in neuraminidase activity was found almost
exclusively in CD8+ cells (Fig. 4B). In
samples in which the CD8+ cells were depleted by
anti-CD8 mAb and complement treatment, there was approximately a
2.5-fold decrease in neuraminidase activity. If CD4+ cells
were depleted, there was only a slight decrease in activity. These
experiments suggest that increased endogenous neuraminidase activity in
CD8+ cells exposed cell surface ligands for PNA by removing
inhibitory sialic acid residues.
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Upon examination of the kinetics of PNA binding to
CD8+ T cells during LCMV infection, a
PNAhighCD8+ T cell population appeared to
persist at day 30 and beyond (greater than day 60). We investigated
whether this population contained LCMV-specific memory CD8+
T cells. We purified CD8+ spleen cells from LCMV-immune
mice (45 days postinfection), as described in Materials and
Methods. These mice have cleared LCMV infection and developed
anti-LCMV memory CD8+ T cells. The CD8+
cells were double stained with PNA and anti-CD8 Ab and sorted by
flow cytometry (Fig. 5A). We isolated two
cell populations, PNAhigh and PNAlow. Each
population was analyzed by limiting dilution to determine the
LCMV-specific CTLp frequency (Fig. 5A). Within the
PNAhigh population, the LCMV-specific frequency was high
(1/102). In contrast, the LCMV-specific CTLp frequency in
the PNAlow population was low (1/9.3 x
103). Thus, virtually all of the LCMV-specific memory CTLp
segregated with the PNAhigh population (99% in the
PNAhigh population and 1% in the PNAlow
population). To further examine the specificity of PNAhigh
and PNAlowCD8 as a function of time, several time points
after infection were tested, and majority of virus-specific CD8 were
PNAhigh at all of the time points (Fig. 5B). These results show that the changes in the
sialylation state of O-glycans on T cell surface
glycoproteins that occur during activation in vivo are maintained on
memory cells. Thus, PNA binding can be used as a marker for memory T
cells. Interestingly, this population of CD8+ memory T
cells that bound PNA did so at a relatively lower level (PNA
intermediate or PNAint) than some of the CD8+ T
cells from the acute stage of LCMV infection (day 8 postinfection)
(Fig. 6). These results suggest that the
level of PNA binding may be useful in discriminating not only betwen
naive and memory cells, but also between effector and memory
CD8+ cells.
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Since changes in PNA binding on CD8+ T cells from
virally infected mice were detected, it was of interest to determine
whether similar changes were taking place on CD4+ T cells
during infection. As shown in Figure 7A, there was an increase in
the number of CD4+PNAhigh spleen cells in mice
acutely infected with LCMV. The number of
CD4+PNAhigh T cells in the spleen in uninfected
(day 0) mice was 1.3 x 106. By day 8 postinfection,
this number increased by more than threefold to 4.3 x
106/spleen. By day 30 postinfection, the number of
CD4+PNAhigh T cells decreased to levels near
what was observed in uninfected mice. The binding of PNA to
CD4+ T cells from VSV- and vaccinia virus-infected mice was
also examined. As was seen with LCMV infection, the
PNAhighCD4+ T cell population increased by
fivefold in VSV-infected mice and eightfold in the vaccinia-infected
mice (Fig. 7B). At day 8 postinfection, there were
6.7 x 106 and 11 x 106
PNAhighCD4+ T cells in the spleens of VSV- and
vaccinia-infected mice. These data showed that changes also occurred in
the sialylation state of surface glycoproteins on mouse
CD4+ T cells during viral infection. To examine whether the
PNAhighCD4 T cells contained virus-specific cells, spleen
cells from LCMV-infected mice (day 8) were cultured for 5 h with
CD4 T cell-specific LCMV peptides (23), followed by intracellular
IFN- stain. The responses of CD4 T cells in PNAhigh and
PNAlowCD4 cells were analyzed. As shown in Figure 8, 7% of the PNAhighCD4
cells were LCMV specific, whereas only 0.4% of PNAlowCD4
cells made IFN- after peptide stimulation. Thus, most of the (93%)
virus-specific CD4 T cells were PNAhigh. Note that neither
PNAhigh nor PNAlowCD4 T cells from naive mice
responded to the peptide stimulation. Hence, these experiments
demonstrate that PNA can also act as a marker for in vivo activated
Ag-specific CD4 T cells.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Spleen cells from mice infected with LCMV were stained with PNA to determine the pattern of expression of the PNA ligand. At the peak of the virus-induced activation and expansion of CD8+ cells and the peak of the CTL activity, the majority of the CD8+ population stained PNAhigh. The increase in PNA binding correlated with the activation of the CD8+ cells, as the PNAhighCD8+ cells were also CD44high. We saw a similar increase in PNAhighCD8+ cells in mice during VSV and vaccinia virus infections. These data show that the increase in PNA binding to CD8+ T cells is a general property of T cell activation during viral infection. Similar changes were also observed in CD4+ T cells.
There are two mechanisms that could account for the increase in
PNA binding to activated T cells. PNA binds to the disaccharide
sequence Galß1,3GalNAc, which is found on O-linked
oligosaccharides attached to glycoprotein structures on the surface of
cells. Sialic acid can be added to this disaccharide structure by two
sialyltransferase enzymes to form the sequence
SA2,3Galß1,3(SA2,6)GalNAc (16). When sialic acid is present,
the PNA binding site is masked. A decrease in the expression or
activity of sialyltransferase enzymes in T cells may result in the
expression of surface glycoproteins that are undersialylated, with more
sites available to bind PNA. Alternatively, sialic acid residues could
be cleaved off nascent or recycled glycoproteins by an endogenous
neuraminidase (12, 27). Thus, an increase in endogenous neuraminidase
activity could account for the increase in PNA binding. In this study,
we showed that T cells from day 8, acutely infected mice had increased
endogenous neuraminidase activity compared with CD8+ cells
from uninfected mice. This suggests that upon activation of these
cells, sialic acid is cleaved off glycoprotein structures, exposing PNA
binding sites.
When CD4+ T cells were depleted from spleen cell samples from day 8 LCMV-infected mice, there was only a slight decrease in neuraminidase activity compared with samples that contained CD4+ T cells. However, we did observe an increase in the CD4+PNAhigh T cell population in LCMV-infected mice. It is possible that due to the smaller number of activated CD4+ T cells compared with activated CD8+ T cells, the neuraminidase assay was not sensitive enough to detect changes in neuraminidase activity in the CD4+ T cell-depleted population, or it may be that the changes in cell surface carbohydrates on CD4+ T cells that we observed are caused by a different mechanism.
When CD8+ T cells from LCMV-immune mice (day 30 or greater postinfection) were stained with PNA, we saw a persistent population of PNA-binding cells. Based on limiting dilution analysis, we showed that the LCMV-specific memory CTLp were contained in this population. Where do these memory cells come from, and when do these changes associated with them develop? Memory cells could first exist as effector cells, binding PNA at a very high level. After clearance of infection, as the population of activated CD8+ cells returns to basal levels, some effector cells may down-modulate their PNA binding, and live on as memory cells. Alternatively, the PNAint cells could be a population that exists separately from the PNAhigh effectors, and after the clearance of infection, the PNAint cells could live on to become memory cells while the PNAhigh cells die.
The T cell surface glycoproteins that bind PNA during activation are currently being explored. Recently, Wu et al. showed that PNA bound to CD43, CD45, and CD8 molecules on mouse thymocytes (28). Furthermore, Casabo et al. showed that during T cell activation, O-linked sugars on the CD8ß chain become desialylated (29). The molecules that bind PNA on activated T cells and memory cells have not been identified. Since the level of PNA binding is higher on effector CD8 T cells (day 8 postinfection) than in memory cells, it is possible that PNA staining may identify cell surface molecules that can distinguish between memory and effector cells. Furthermore, the functional importance of the alteration in sialylation needs to be examined. Carbohydrate structures attached to surface glycoproteins play a role in T cell circulation, trafficking, and adhesion (30). The glycosylation changes documented in this study could be important for trafficking and localization of memory cells and effector cells to sites of Ag presentation. Alterations in cell surface sialylation may also affect T cell recognition of APCs, or interactions with accessory molecules. For example, CD23 on B cells has been shown to bind to the Galß1,3GalNAc sequence (31). The Galß1,3GalNAc sequence can be masked by the addition of sialic acid, resulting in the inhibition of CD23 binding. Moreover, similar to what we documented in this study, changes in the glycosylation pattern on the surface of B cells have been shown to occur specifically on the surface of Ag-specific B cells in germinal centers of mouse lymph nodes (32, 33). The changes in sialylation documented in this study may play a role in T cell signaling by acting through such molecules as CD8 and CD43 (29, 34). The dynamic modulation of T cell surface glycosylation indicates that these changes affect T cell function, in addition to allowing the phenotypic discrimination between naive and effector/memory T cells.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Rafi Ahmed, Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.E-mail address:
3 Abbreviations used in this paper: PNA, peanut agglutinin; CTLp, cytotoxic T lymphocyte precursor; int, intermediate; LCMV, lymphocytic choriomeningitis virus; 4-MU, 4-methylumbelliferone; 4-MU-NANA, 4-methylumbelliferyl-N-acetylneuraminic acid; PE, phycoerythrin; PFU, plaque-forming unit; VSV, vesicular stomatitis virus.
Received for publication June 4, 1997. Accepted for publication March 16, 1998.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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2,3-sialyltransferase expression correlates with conversion of peanut agglutinin (PNA)+ to PNA- phenotype in developing thymocytes. J. Biol. Chem. 268:3801.This article has been cited by other articles:
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T. M. Onami, M.-Y. Lin, D. M. Page, S. A. Reynolds, C. D. Katayama, J. D. Marth, T. Irimura, A. Varki, N. Varki, and S. M. Hedrick Generation of Mice Deficient for Macrophage Galactose- and N-Acetylgalactosamine-Specific Lectin: Limited Role in Lymphoid and Erythroid Homeostasis and Evidence for Multiple Lectins Mol. Cell. Biol., July 15, 2002; 22(14): 5173 - 5181. [Abstract] [Full Text] [PDF]
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T. M. Onami, L. E. Harrington, M. A. Williams, M. Galvan, C. P. Larsen, T. C. Pearson, N. Manjunath, L. G. Baum, B. D. Pearce, and R. Ahmed Dynamic Regulation of T Cell Immunity by CD43 J. Immunol., June 15, 2002; 168(12): 6022 - 6031. [Abstract] [Full Text] [PDF]
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D. J. Topham, M. R. Castrucci, F. S. Wingo, G. T. Belz, and P. C. Doherty The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia J. Immunol., December 15, 2001; 167(12): 6983 - 6990. [Abstract] [Full Text] [PDF]
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C. D. Chung, V. P. Patel, M. Moran, L. A. Lewis, and M. C. Miceli Galectin-1 Induces Partial TCR {zeta}-Chain Phosphorylation and Antagonizes Processive TCR Signal Transduction J. Immunol., October 1, 2000; 165(7): 3722 - 3729. [Abstract] [Full Text] [PDF]
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F. Porras, R. Lascurain, R. Chavez, B. Ortiz, P. Hernandez, H. Debray, and E. Zenteno Isolation of the receptor for Amaranthus leucocarpus lectin from murine naive thymocytes Glycobiology, May 1, 2000; 10(5): 459 - 465. [Abstract] [Full Text] [PDF]
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L. E. Harrington, M. Galvan, L. G. Baum, J. D. Altman, and R. Ahmed Differentiating between Memory and Effector CD8 T Cells by Altered Expression of Cell Surface O-Glycans J. Exp. Med., April 3, 2000; 191(7): 1241 - 1246. [Abstract] [Full Text] [PDF]
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 M. Saifuddin, M. L. Hart, H. Gewurz, Y. Zhang, and G. T. Spear Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1 J. Gen. Virol., April 1, 2000; 81(4): 949 - 955. [Abstract] [Full Text]
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 S Sabri, M Soler, C Foa, A Pierres, A Benoliel, and P Bongrand Glycocalyx modulation is a physiological means of regulating cell adhesion J. Cell Sci., January 5, 2000; 113(9): 1589 - 1600. [Abstract] [PDF]
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M. K. Slifka and J. L. Whitton Activated and Memory CD8+ T Cells Can Be Distinguished by Their Cytokine Profiles and Phenotypic Markers J. Immunol., January 1, 2000; 164(1): 208 - 216. [Abstract] [Full Text] [PDF]
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A. Cerwenka, T. M. Morgan, and R. W. Dutton Naive, Effector, and Memory CD8 T Cells in Protection Against Pulmonary Influenza Virus Infection: Homing Properties Rather Than Initial Frequencies Are Crucial J. Immunol., November 15, 1999; 163(10): 5535 - 5543. [Abstract] [Full Text] [PDF]
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D. A. Carlow, B. Ardman, and H. J. Ziltener A Novel CD8 T Cell-Restricted CD45RB Epitope Shared by CD43 Is Differentially Affected by Glycosylation J. Immunol., August 1, 1999; 163(3): 1441 - 1448. [Abstract] [Full Text] [PDF]
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M. Kaufmann, C. Blaser, S. Takashima, R. Schwartz-Albiez, S. Tsuji, and H. Pircher Identification of an {alpha}2,6-sialyltransferase induced early after lymphocyte activation Int. Immunol., May 1, 1999; 11(5): 731 - 738. [Abstract] [Full Text] [PDF]
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d30) mice. At day 8 post-LCMV infection, there is a
population of PNAhighCD8+ T cells
(>103 intensity) that is missing in LCMV-immune mice.
Numbers indicate percentage of cells in each quadrant.
