| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
T Cells1
*
Department of Microbiology, University of Texas Health Science Center, San Antonio, TX 78284; and
Corporación para Investigaciones Biológicas, Medellín, Colombia
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
T cells), and adaptive immune responses (
ß T cells and B
cells) in infected mice. T cells are the predominant T cell
population. A cell-mediated Th1 pathway of cytokine expression is
evident in contrast to the previously described Th2 phenotype induced
in the periphery. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Much of the pathology of NCC is thought to be due to the host immune response to the metacestode in the brain (13, 14). Therefore, a careful characterization of the immune response is critical for understanding the disease process. This has been hampered by the difficulty in studying CNS immune responses in patients and the complexity of the associated biology. The immune response is thought to vary depending on the incubation period, the number and location of cysts in the brain, and the stage of the cyst (alive or in any of various stages of disintegration) (13, 14, 15). Because of the number of variables, we sought to develop a mouse model in which a systematic study of the immune response could be performed.
T. solium is not infectious in mice. Therefore, a related cestode parasite, Mesocestoides corti, was used (16, 17, 18, 19, 20). In nature, M. corti ova are thought to be ingested by terrestrial arthropods (20). An intermediate host, e.g., lizard or mouse, then consumes the arthropod, whereby the oncosphere develops into a mature larva or metacestode. Upon ingestion of the intermediate host by a carnivorous mammal such as a dog, cat, or skunk, a mature intestinal tapeworm develops, releasing eggs and perpetuating the life cycle. A similar life cycle is observed with T. solium in cysticercosis (2). In NCC, however, individuals consume the ova, which appears to result in an immature larva migrating to the brain and developing into a metacestode. An immune response to the metacestode is then elicited, causing much of the pathology (1, 2).
To parallel the human disease of NCC as much as possible, metacestodes
from M. corti were injected intracranially, avoiding
penetration of the brain tissue. Similar to T. solium
larvae, they were found to be highly invasive, infiltrating within days
ventricular and subarachnoid spaces as well as the parenchyma. Animals
were killed at various times after infection, and the immune cells and
cytokines were analyzed by in situ immunohistochemistry. One of the
most interesting aspects of the response was an extensive accumulation
of T cells that remained throughout the course of the study.
Importantly, the infection-induced CNS immune response proceeded
through a typical innate response, followed by an early induced
response of NK cells and T cells and, eventually, an adaptive
immune response. Similar to our analyses of brain specimens from NCC
patients (21), the cytokine response was typical of a Th1 or
inflammatory response. The study shows that this animal model
represents a prototype for NCC and will be invaluable for further
analysis of the immune response and the associated pathology.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Female BALB/c mice were purchased from the National Cancer Institute Animal Program (Bethesda, MD). Animal experiments were conducted under the guidelines of the University of Texas System, The United States Department of Agriculture, and the National Institutes of Health.
Parasites and inoculations
M. corti metacestodes were used in all experiments. Parasites were maintained by serial i.p. inoculations of 8- to 12-wk-old female BALB/c mice with 50–75 metacestodes in 0.5 ml of HBSS (16, 22).
For intracranial inoculations, parasites were aseptically collected
from the i.p. cavity of mice that had been infected for about 6 mo.
Harvested parasites were extensively washed in HBSS. Analysis of number
and viability of organisms was determined by direct stereoscopic
examination. The metacestodes (
40 parasites) were then suspended in
60 µl of sterile HBSS and injected intracranially into 3–5-wk-old
female BALB/c mice using 1-ml syringes and a 25-gauge needle (23). The
needle was inserted to a 2-mm depth at the junction of the superior
sagittal and the transverse sutures. This allows insertion of the
needle into a protective cuff avoiding penetration of the brain tissue
(23). Control mice were injected with 60 µl of sterile HBSS using the
same protocol. Before intracranial inoculation, mice were anesthetized
with a mixture of phenobarbital (1.2 mg) and xylazine (0.16 mg) in 100
µl. At several times after inoculation, animals were sacrificed and
assessed for extent of infection and various immune parameters (see
below). Before sacrifice, animals were anesthetized with a mixture of
ketamine (6 mg) and xylazine (0.8 mg) and perfused through the left
ventricle with 20 ml of cold PBS.
Dye exclusion assay
Integrity of the blood-brain barrier (BBB) was assessed 10 min and 24 h after intracranial inoculation. Ten minutes before sacrifice, mice were injected in the tail vein with 100 µl of 4% Evans blue dye in PBS, pH 7.4 (24). Blood samples were taken by cardiac puncture using 3% sodium citrate in H2O as an anticoagulant. Then mice were perfused through the left ventricle. Brains were removed, homogenized for 10 s in 3 ml of PBS using an Omni 2000 homogenizer (Omni International, Waterbury, CT), and centrifuged for 20 min at 750 x g. Supernatants were again centrifuged for 30 min at 2500 x g, and optical densities were read at 610 nm. For blood samples, 100 µl of plasma was used. A standard curve was used to quantify the amount of dye present in the brain and plasma as previously described (24, 25, 26).
Tissue processing
The brain was immediately removed from perfused animals, embedded in optimal cutting temperature compound, and snap frozen. Serial horizontal cryosections 10 µm in thickness were placed on silane preparation slides (Sigma, St. Louis, MO). One in every four slides was fixed in formalin for 12 min at room temperature and stained with hematoxylin and eosin (H&E). The remainder of the slides was air dried overnight and fixed in fresh acetone for 20 s at room temperature. Acetone-fixed sections were wrapped in aluminum foil and stored at -80°C or processed immediately for immunohistochemistry.
H&E staining
After formalin fixation, slides were washed twice in deionized water, stained 30 s in hematoxylin, and washed in distilled water for 1.5 min. Slides were submerged in 0.5% HCl and then in 0.1% NH4(OH)2. Tissues were dehydrated in 95% ethanol for 1 min and stained in eosin for 15 s followed by a 2-min treatment with 95% and 100% ethanol each. Slides were allowed to air dry. They were then submerged in xylene for 3 min and mounted using Pro-Texx mounting medium (Baxter Diagnostics, Deerfield, IL). By light microscopy, the number and location of parasites were assessed, as well as the presence or absence of mononuclear infiltrates.
Monoclonal Abs
Biotinylated Abs were used to identify particular murine
leukocytes and cytokines by immunohistochemistry. Biotinylated Abs
purchased from PharMingen (San Diego, CA) include 145-2C11
(anti-CD3
), RM4-5 (anti-CD4), 53-6.7 (anti-CD8), GL3
(pan-anti-), H57-597 (pan-anti-ß), 5E6
(anti-NK), M1/70 (anti-Mac1), 1D3 (CD19 and B cells), 25-9-17
(which reacts with both I-Ad and I-Ab), 536
(anti-V5 (V3 according to nomenclature developed by
Garman et al. (27)), UC3–10A6 (anti-V4, or V2 by Garman et
al. (27) nomenclature), GL2 (anti-V4), XMG1.2
(anti-IFN-), SXC-1 (anti-IL-10), BVD6-24G2 (anti-IL-4),
MP5-32C11 (anti-IL-6), JES6-5H4 (anti-IL-2), G297-289
(anti-IL-12), and G277-3960 (anti-IL-15). The 1400-24.17 mAb
(anti-IL-1ß) was purchased from Endogen (Woburn, MA). The mAb 17C
(anti-6.3) was kindly donated by Dr. Simon Carding (University
of Pennsylvania, Philadelphia, PA). The G297-289 purified mAb
(anti-IL-12), which was obtained from PharMingen, and the purified
anti-mouse polyclonal Ab against the IL-13 from R&D Systems
(Minneapolis, MN) were biotinylated using the protocol previously
described (21). Each of the mAbs was initially titrated on spleen
sections of infected mice. A dilution was chosen to give maximum
sensitivity with no background staining. Some Abs were completely
negative on brain specimens but known to be active by positive staining
on spleen sections.
Immunohistochemistry
Frozen sections were thawed for 60 min at room temperature and postfixed in acetone for 10 min at room temperature. Sections were then hydrated in 0.1% BSA in PBS for 6 min. To block binding by endogenous avidin and biotin, sections were treated with an avidin-biotin blocking kit (Vector Laboratories, Burlingame, CA) according to the manufacturer’s instructions. Sections were also blocked for nonspecific Ig binding by incubation for 30 min with a 1:10 dilution of normal serum from the appropriate host species. Sections were then incubated for 1 h at 37°C, with specific Abs diluted in 3% host normal serum in HBSS. This was followed by a 30-min incubation with the streptavidin-alkaline phosphatase conjugate (Kirkegaard & Perry Laboratories, Gaithersburg, MD). Between each incubation step of the protocol, the slides were rinsed three times in PBS for 3 min each. The reaction product was developed using the alkaline phosphatase substrate kit (Vector Laboratories) according to the manufacturer’s instructions, which produced a red stain.
Sections were counterstained with an alcian blue-methyl green solution (0.25% alcian blue and 0.25% methyl green in 1 mM sodium acetate, pH 5.2) for 1 min and then dehydrated in solutions of increasing ethanol concentrations (75%, 95%, and 100%, 1 min per solution). After 3 min in xylene, sections were mounted with Pro-Texx mounting medium (Baxter Diagnostics).
A semiquantitative analyses of the cellular infiltrates was done by counting the number of cells of a given cell type/cytokine per section. An analysis of all of the markers required many sections. Serial sections can vary in the extent of exposed infiltrate. Therefore, comparison of actual numbers of cells staining with different markers is only semiquantitative. This problem was alleviated somewhat by testing all markers on two infected animals. Positive cells were counted on an entire section. The area of the sections ranged from 50 to 78 mm2. The results were scored, in positive cells per section, as follows: +, 1–100; ++, 100–300; +++, 300–500; and ++++, >500. The results shown represent the average of two mice.
Transmission electron microscopy
A mouse brain infected for 3 wk was processed for analysis by electron microscopy. The brain was perfused with 20 ml of cold PBS and then fixed in a standard phosphate-buffered mixture (84 mM NaH2PO4, 68 mM NaOH) of 4% formaldehyde (v/v) and 1% glutaraldehyde (v/v). From 1-mm2 pieces, ultrathin 75-nm sections were collected on a 150-mesh copper grid and stained with saturated aqueous uranyl acetate and Reynolds lead citrate (Electron Microscopy Sciences, Fort Washington, PA). Photographs were taken using a JEOL 100CX electron microscope (JEOL, Peabody, MA).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Mice were inoculated with approximately 40 metacestodes, since this number of organisms resulted in infection of essentially all inoculated animals. With this dose, animals usually began to show neurological symptoms including staggering and abnormal vestibular functions (e.g., abnormal landing foot splay). Even though symptoms started by 3–5 wk postinoculation (p.i.), mice did not usually succumb until about 13 wk. We are currently experimenting with lower numbers of organisms so that animals infected for longer periods can be analyzed.
Serial horizontal sections spaced every 10 µm were stained with H&E
to assess the number of larvae, location, and presence of cellular
infiltrate. Table I
shows the number and
location of organisms. Within the first few days of infection, many of
the organisms remained outside the brain and were lost when the brain
was removed for analysis. By 1 wk p.i., the majority of parasites were
extraparenchymal (in the ventricles, leptomeninges, and subarachnoid
spaces). However, by 3 wk p.i., approximately half of the organisms had
penetrated the parenchyma. Fig. 1A shows a larva invading
brain parenchyma. The percentage of organisms located in parenchymal
tissue continued to increase with time postinfection.
|
|
B). In
contrast, the infiltration of mononuclear cells into the parenchyma was
slower, and at the earliest times postinfection many parenchymal
parasites showed no evidence of associated infiltrate (Fig. 1C). This was confirmed by immunohistochemistry (data not
shown). Temporal appearance of specific cell types p.i. in extraparenchymal spaces
To characterize the nature of the cellular infiltrate,
immunohistochemistry was performed on brain specimens at various times
after infection. Control HBSS-injected mice were also analyzed, but
since no infiltrate was observed, except in the animal described above,
these negative data are not included in any of the tables. Because of
the more rapid infiltration of cells into the extraparenchymal spaces
compared with the parenchyma, these two areas were analyzed separately
for the appearance of distinct cell types. The data provided in Table II indicate that by 2–3 days p.i. the
CNS immune response consisted of neutrophils (detected by H&E
staining), macrophages (Mac-1+), T cells, and NK cells. Most
dramatic was the infiltration of T cells (Fig. 1B).
The cellular infiltrate was also analyzed by electron microscopy.
Polymorphonuclear neutrophils (PMN), macrophages, and plasma
cells were present in ventricular (Fig. 1D) and parenchymal
infiltrates. MHC class II expression (I-Ad-positive cells)
was also observed consistent with the presence of macrophages. The
absence of a direct correlation between the frequency of
CD3+ cells and that of T cells has been noted by
other investigators and is likely due to sensitivity/accessibility
issues (28). Initially, the number of mononuclear cells was found to be
relatively small, but by 1 wk of infection, the accumulation of cells
surrounding organisms was substantial (>300–500 cells/brain section).
Moreover, by 5–7 days p.i., ß T cells were detectable, as well as
relatively small numbers of CD19+ B cells. Although both
CD4+ and CD8+ T cells were detected,
CD4+ cells consistently outnumbered CD8+ cells
by approximately 2:1. Interestingly, T cells continued to be a
predominant cell type throughout the course of the 13-wk study.
|
During the first week of infection, very few mononuclear cells
were found in the parenchyma despite the presence of metacestodes
(Table III). Only granulocytes and
macrophages were present and in substantially fewer numbers compared
with the extraparenchyma spaces. T cells were detected by 3 wk
and continued to be found for the duration of the study.
CD4+ and CD8+ cells were not detected until 5
wk p.i. Although there were a few NK cells detected in the parenchyma
in the absence of an associated organism, no NK cells were detected in
the direct vicinity of a metacestode. Macrophages and T cells could
also be detected in such areas devoid of parasites. The mechanism for
the presence of immune cells in the absence of an organism is not clear
to us. Because entire brains were serially sectioned and the location
of all metacestodes was determined, we are confident that the immune
cells observed were not in the vicinity of any parasite, even the ones
out of the plane of the section being observed. It is possible, though,
that migrating organisms leave parasite Ags behind that can elicit an
immune response.
|
T cell infiltrate
To ensure that our pan-anti- T cell reagent was not
picking up some cross-reactive cell type and to determine the diversity
associated with the T cell response, various Abs to
variable regions were used in immunohistochemistry. The results (Table IV) indicate that the V4-positive T
cells (Fig. 1E) and V4-positive T cells substantially
contributed to the T cell population. V5 cells and V6.3
T cells were detected less frequently.
|
To further characterize the cellular response due to CNS infection
by M. corti metacestodes, the production of several
cytokines was assessed by in situ immunohistochemistry. Cytokines
detected in ventricles and subarachnoid space were predominantly IL-2,
IL-12, IL-15, and IFN- (Table V). IL-2
and IL-12 appeared after 2 days p.i., IL-15 by day 5 p.i., and
IFN- by 1 wk p.i. (Fig. 1F). All four cytokines
colocalized (adjacent serial sections) to areas where
TCR+ cells and macrophages were present. These four
cytokines appeared to be the predominant cytokines produced throughout
the course of infection. IL-4 was detected after 1 wk p.i. in low
levels. There was sporadic appearance of a few TNF-- and
IL-10-producing cells later in infection. However, several cytokines
were not detected, including IL-1, IL-6, and IL-13. The absence of key
proinflammatory cytokines, including IL-1 and IL-6, is of interest.
Moreover, the Th2 cytokines, IL-4 and IL-10, highly induced during
helminth infection were not predominantly expressed, and IL-13, which
is also an important cytokine in Ab-mediated immune responses, was
undetectable at all time points tested.
|
were
present at certain time points and in low abundance (Table VI).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The purpose of this study was to develop an animal model for NCC, one of the most common parasitic infections of the CNS. M. corti metacestode was chosen as the infecting organism since it is a cestode like T. solium, is amenable to intracranial injections, and is the form of cestodes that encysts the brain in NCC. We are also in the process of testing a murine Taenia species, T. crassiceps. The metacestode form of this organism, however, is large and appears to be less invasive compared with M. corti. Nevertheless, studies with T. crassiceps will help determine the generality of the immune response to platyhelminths in the CNS.
The results indicate that within 2–3 days M. corti larvae have already invaded both parenchymal and extraparenchymal areas of the brain. The majority of the invading organisms are first found in the extraparenchymal spaces. This seems logical, since invasion of the parenchyma probably involves induction of the enzymatic machinery (e.g., proteolytic enzymes) necessary to penetrate the brain tissue. By 3–5 wk of infection, there is an equal distribution of organisms in parenchyma and extraparenchymal spaces, but eventually the majority of the organisms appear to enter the parenchyma. This parallels the results found in humans with T. solium, most of whom present with parenchymal cysts (2).
An interesting aspect of these studies is that there appears to be a
natural progression of innate, early induced, and adaptive immune
responses. ß T cells are delayed by several days, particularly in
the parenchyma, compared with cells ascribed to the innate and early
induced responses. This is important, because it has been proposed that
only memory T cells pass through the BBB and remain in the CNS, and
only if the relevant Ags are present (37). It has been further
proposed that Ag-activated memory T cells in the brain then
initiate/amplify the inflammatory response as a result of CNS
infections or autoimmune diseases such as multiple sclerosis or
experimental allergic encephalitis (38, 39, 40). In the model described
here, the first encounter with the Ag (organism) is in the CNS, and the
results suggest that under these circumstances the CNS response begins
with innate immunity similar to a peripheral infection. Given the
extent of neurotropism associated with T. solium, especially
with the organisms endemic to Mexico and Central and South America (4, 12), it is possible that a similar situation can occur in NCC. To
address this further, we plan to first infect mice with M.
corti i.p. and follow the infection with an i.c. inoculation at a
later time point to see whether this changes the course of the CNS
immune response. It will also be important to examine cell activation
markers. Also of potential relevance, these types of organisms are
known to produce excretory/secretory molecules (41, 42, 43). The extent to
which these molecules enter the periphery and induce a systemic immune
response with possible migration of activated immune cells back to the
CNS is not known.
The cytokines produced by infiltrating cells in the CNS during M.
corti infection are indicative of a cell-mediated, Th1 type of
response (44, 45). Thus, the cytokines detected include IL-2, IL-12,
IL-15, IFN-, and TNF-. IL-4, the major indicator of the Th2
Ab/eosinophilia immune pathway (45), was detected in low levels during
the first weeks of infection. This correlates with the presence of low
numbers of B cells present after the first week postinfection.
Therefore, a complete dichotomy in the Th1 and Th2 types of responses
was not observed. This is of interest since M. corti is a
platyhelminth that typically induces a strong Th2 response replete with
an IgG1, IgE hypergammaglobulinemia, and eosinophilia when the
infection is a peripheral one (16, 22). In a previous study, we
analyzed human brain specimens from four NCC patients for the cell
types and cytokines present (21). Importantly, the results were similar
in that a Th1-type, cell-mediated response predominated. Thus, it is
possible that with helminth infections the microenvironment of the CNS
favors a Th1 response, whereas the systemic environment favors a Th2
response.
IL-12 is considered to be a pivotal cytokine for inducing the cell-mediated, Th1-type pathway (44). Recently, it has been shown that IL-12 is protective in vesicular stomatitis virus CNS infections (46). IL-12 appears to directly activate neurons as well as astrocytes and microglia to produce nitric oxide synthase. Therefore, it will be very important to determine in our studies whether IL-12 is involved in immunoprotection and the role of brain-resident cells that may be influenced by the infection-induced cytokine microenvironment.
There are several factors that contribute to the immune privilege status of the normal brain, especially the BBB. Even when the BBB was breached during infection, there was a substantial delay in the appearance of immune cells and associated cytokines in the parenchyma compared with the extraparenchymal spaces. Granuloma formation was also delayed. When M. corti metacestodes are injected i.p., the liver is the main organ that is encysted (16). Under these circumstances, evidence of mature granuloma formation is found by the first 2–3 wk of infection. However, in this study granuloma formation was not observed. Interestingly, mature granulomas were not found in the human specimens either (21), although magnetic resonance imaging scans of NCC patients often exhibit calcifications (1, 2, 47), suggesting that granulomas eventually form (48). Therefore, it will be important to examine mice injected with fewer organisms and reexamine the cytokine response and the potential appearance of granulomas after 6 mo to 1 year of infection.
One of the most interesting aspects of this CNS infection is the
dramatic accumulation of T cells. A T cell response has
been described in a number of different types of infections including
bacteria, viruses, and parasites (49). Although there is evidence for a
late dominance of T cells in murine influenza (50), T
cells typically appear early in the infectious process (51, 52).
Because of their restricted repertoire, they are thought to provide a
first line of defense and respond to a limited number of Ags. However,
little is known regarding effector functions. Earlier studies suggested
that T cells might respond to a common stress response (53).
This is of interest, since our previous work demonstrated that M.
corti metacestodes actively secrete a number of molecules,
including at least two heat shock proteins (42, 43). More recently, it
has been shown that T cells can respond to nonpeptide Ags such
as alkyl phosphates (54) and that the crystalline structure of the
TCR combining site more closely resembles an Ab (55). Thus, it
will be important to determine the nature of the antigenic stimulus in
this infection.
Based on the V region analysis, it does not appear that the infection
is inducing a single subset of T cells. However, the
predominance of V4, V4, and V6.3 suggests that the source of
T cells be mainly from lymphoid tissue and not the epithelium
(49). The role of T cells in the CNS defense will also be
important to assess. Although T cells have been described as a
minor population in multiple sclerosis lesions (56), to our knowledge,
they have not been described as a major cell type in inflammatory
infiltrates in the brain. It is possible that the early response in the
CNS helps to establish a cytokine microenvironment that promotes the
Th1 pathway. Consistent with this, immunocytochemistry of serial
sections indicate that T cells colocalized to IL-2, IFN-, and
IL-12. Since other cell types are present, we are in the process of
performing double labeling experiments. T cells have been
described previously to produce IL-2 and IFN- (57) and are a likely
source of these cytokines early in the infection. Also of interest is
the up-regulation of IL-15 in the infection, since this cytokine has
been shown to cause proliferation and prevent apoptosis of T
cells (58). IL-15 has also been shown to increase the cytotoxicity of
granular lymphocytes in patients with lymphoproliferative disease of
granular lymphocytes (59). Since the T cells often associate
with the organism, we are currently looking for the presence of
cytotoxic molecules (e.g., perforins) that would be indicative of a
cytotoxic role.
In summary, this study describes a viable model for the study of the
human disease NCC. M. corti metacestodes are shown to invade
the CNS, resulting in a multifaceted immune response that includes
innate, early induced, and adaptive immunity. Although an analysis of
the kinetics of the immune response in NCC patients is not possible,
the cell types identified in surgical specimens are essentially the
same as shown here (21). Heterogeneity in cell types was observed in
the different immune lesions, but among the patients analyzed, the cell
types identified included macrophages, neutrophils, NK cells,
CD4+ and CD8+ T cells, and plasma cells. Thus,
the results were consistent with cells characteristic of early and late
immune responses (21). A prominent feature of the animal model is a
striking T cell response. It is not known yet whether human NCC
exhibits a similar T cell response, since our human studies were
completed before our knowledge of the T cell response in mice.
We plan to determine this as soon as we obtain human surgical specimens
from Dr. Antonio Enciso (Instituto Mexicano del Seguro Social, Mexico
City, Mexico). Another important characteristic of the animal
model is that the predominant immune response follows a Th1 pathway.
This provides another parallel to NCC, in which the cells and cytokines
identified in the human specimens were most characteristic of a Th1
pathway. Thus, IL-12 was found in all immune lesions analyzed and IL-2
and IFN- were also prominent. In contrast, IL-4 was not detected in
any of the inflammatory infiltrates of human specimens analyzed (21).
The mice also develop neurological complications, as do many NCC
patients, and it will be important to correlate neurological symptoms
with the immunopathology. Taken together, the animal model described
here should provide a unique opportunity for delineating
immunoregulatory and pathogenic mechanisms in NCC.
|
Acknowledgments |
|---|
6.3 Ab. |
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Judy M. Teale, Department of Microbiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284. E-mail address:
3 Abbreviations used in this paper: CNS, central nervous system; NCC, neurocysticercosis; H&E, hematoxylin and eosin; p.i., postinoculation; BBB, blood-brain barrier; PMN, polymorphonuclear neutrophils.
Received for publication June 26, 1998. Accepted for publication September 25, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
genes. Cell 45:733.[Medline]
is not required in the IL-12 response to vesicular stomatitis virus infection of the olfactory bulb. J. Immunol. 159:3444.[Abstract]
/ Cells. Annu. Rev. Immunol. 11:637.[Medline]
+ T cells in vivo. J. Exp. Med. 172:1225. and ß bearing T cells in the peritoneal cavity during an intraperitoneal infection with Leisteria monocytogenes. J. Immunol. 20:533.
and interleukin-4 in response to Th1- and Th2-stimulating pathogens by T cells in vivo. Nature 373:255.[Medline]
T cells. Science 279:1737. domain of the human T-cell receptor. Nature 391:502.[Medline]
T cell receptor repertoire in brain lesions of patients with multiple sclerosis. J. Neuroimmunol. 46:225.[Medline]
- T cell antigen receptor. Chem. Immunol. 53:32.[Medline]
- T cell receptor in mice. Eur. J. Immunol. 27:2885.[Medline]
This article has been cited by other articles:
|
|
 |
|
  B. B. Mishra, U. M. Gundra, K. Wong, and J. M. Teale MyD88-Deficient Mice Exhibit Decreased Parasite-Induced Immune Responses but Reduced Disease Severity in a Murine Model of Neurocysticercosis Infect. Immun., December 1, 2009; 77(12): 5369 - 5379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Alvarez, J. Krishnamurthy, and J. M. Teale Doxycycline Treatment Decreases Morbidity and Mortality of Murine Neurocysticercosis: Evidence for Reduction of Apoptosis and Matrix Metalloproteinase Activity Am. J. Pathol., August 1, 2009; 175(2): 685 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Uddin, H. H. Garcia, R. H. Gilman, A. E. Gonzalez, and J. S. Friedland Monocyte-Astrocyte Networks and the Regulation of Chemokine Secretion in Neurocysticercosis J. Immunol., September 1, 2005; 175(5): 3273 - 3281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Cardona, P. A. Gonzalez, and J. M. Teale CC Chemokines Mediate Leukocyte Trafficking into the Central Nervous System during Murine Neurocysticercosis: Role of {gamma}{delta} T Cells in Amplification of the Host Immune Response Infect. Immun., May 1, 2003; 71(5): 2634 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Cardona and J. M. Teale {gamma}/{delta} T Cell-Deficient Mice Exhibit Reduced Disease Severity and Decreased Inflammatory Response in the Brain in Murine Neurocysticercosis J. Immunol., September 15, 2002; 169(6): 3163 - 3171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Restrepo, J. I. Alvarez, J. A. Castano, L. F. Arias, M. Restrepo, J. Trujillo, C. H. Colegial, and J. M. Teale Brain Granulomas in Neurocysticercosis Patients Are Associated with a Th1 and Th2 Profile Infect. Immun., July 1, 2001; 69(7): 4554 - 4560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rajan, V. C. Asensio, I. L. Campbell, and C. F. Brosnan Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of {gamma}{delta} T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System J. Immunol., February 15, 2000; 164(4): 2120 - 2130. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
