Regulation of t cell responses during central nervous system viral infection

Irani, David N.; Griffin, Diane E.

doi:10.1016/s0065-3527(01)56007-8

Cited by 28 publications

(31 citation statements)

References 58 publications

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“…Large numbers of IFN-␥-and TNF-␣-producing CD4 ϩ and CD8 ϩ cells were detected whereas IL-17-and IL-10-producing cells were much less prevalent, indicating that both the CD4 ϩ and CD8 ϩ cell populations appeared to be participating in a predominantly Th1-skewed response. IL-2 production was minimal, in accordance with previous findings for Sindbis infection (26). The numbers of IFN-␥-and TNF-␣-producing CD4 ϩ and CD8 ϩ cells were roughly equivalent at day 8, but by day 15 the number of CD8 ϩ cells producing both cytokines was approximately 2-fold higher than the number of CD4 ϩ cells producing both cytokines, reflecting an overall increase in the ratio of total CD8 ϩ cells to CD4 ϩ cells at this time point.…”

Section: Cd4supporting

confidence: 92%

T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody

Brooke

Deming

Whitmore

et al. 2010

J Virol

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Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus of the genusAlphavirus that is responsible for a significant disease burden in Central and South America through sporadic outbreaks into human and equid populations. For humans, 2 to 4% of cases are associated with encephalitis, and there is an overall case mortality rate of approximately 1%. In mice, replication of the virus within neurons of the central nervous system (CNS) leads to paralyzing, invariably lethal encephalomyelitis. However, mice infected with certain attenuated mutants of the virus are able to control the infection within the CNS and recover. To better define what role T cell responses might be playing in this process, we infected B cell-deficient MT mice with a VEEV mutant that induces mild, sublethal illness in immune competent mice. Infected MT mice rapidly developed the clinical signs of severe paralyzing encephalomyelitis but were eventually able to control the infection and recover fully from clinical illness. Recovery in this system was T cell dependent and associated with a dramatic reduction in viral titers within the CNS, followed by viral persistence in the brain. Further comparison of the relative roles of T cell subpopulations within this system revealed that CD4 ؉ T cells were better producers of gamma interferon (IFN-␥) than CD8 ؉ T cells and were more effective at controlling VEEV within the CNS. Overall, these results suggest that T cells, especially CD4 ؉ T cells, can successfully control VEEV infection within the CNS and facilitate recovery from a severe viral encephalomyelitis.

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Section: Cd4supporting

confidence: 92%

T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody

Brooke

Deming

Whitmore

et al. 2010

J Virol

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“…This latter observation is in contrast to Sindbis virus encephalitis, an acute, self-limited viral infection of the CNS, in which i.c. leukocytes did not suppress splenic T cell responses (8). Currently, the reason for these divergent findings remains unresolved; however, the observation that i.c.…”

Section: Discussionmentioning

confidence: 99%

Phenotype and Regulation of Persistent Intracerebral T Cells in Murine Toxoplasma Encephalitis

Schlüter

Meyer

Kwok

et al. 2002

The Journal of Immunology

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Toxoplasma gondii is a parasite causing asymptomatic, persistent encephalitis. Protective CD4 and CD8 T cells are recruited to and accumulate in the brain in acute Toxoplasma encephalitis (TE), with slowly decreasing numbers in chronic TE. It is unclear how the size of the intracerebral T cell pool is regulated. Conceivably, permanent recruitment, proliferation, and apoptosis may be involved. We observed that in murine TE recruitment of T cells to the brain was terminated in chronic TE. In vivo 5-bromo-2′-deoxyuridine incorporation and in vitro T cell proliferation experiments revealed that intracerebral T cells did not proliferate, which was explained by the expression of the cell cycle inhibitors p21Waf/cip1 and p27Kip1 and the inhibitory activity of intracerebral F4/80+ cells. TUNEL staining detected apoptotic T cells at low frequency corresponding to an increased expression of the anti-apoptotic molecules Bcl-2 and Bcl-xL and a reduced expression of the pro-apoptotic molecules Bad, Bax, and Fas ligand in CD4 and CD8 T cells. During progression from acute to chronic TE, both CD4 and CD8 T cells down-regulated CD45RB expression and expressed a differential pattern of cytokines. From these experiments it is concluded that the number of intracerebral T cells increases by recruitment of T cells during acute infection, whereas proliferation of intracerebral T cells does not play a role. In chronic TE, T cell recruitment is terminated, the phenotype of intracerebral T cells changes, and their number is gradually downsized by low level apoptosis, which, however, does not completely resolve the T cell infiltrates.

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“…After MHV-JHM infection, CD8 ϩ T cells persisted in the CNS and maintained their ability to produce IFN-␥, but they gradually lost cytotoxic activity (50). In another system, T cells responding to Sindbis virus infection in the CNS down-regulated IL-2 production and lost their ability to proliferate after entering the brain (51). Transfer of LCMV-primed lymphocytes to mice chronically infected with LCMV resulted in much slower clearance of infectious virus from the CNS than from peripheral organs such as spleen, liver, and lung.…”

Section: Discussionmentioning

confidence: 99%

Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

Matthews

Weiss

Shlomchik

et al. 2001

The Journal of Immunology

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Intracerebral inoculation with mouse hepatitis virus strain A59 results in viral replication in the CNS and liver. To investigate whether B cells are important for controlling mouse hepatitis virus strain A59 infection, we infected muMT mice who lack membrane-bound IgM and therefore mature B lymphocytes. Infectious virus peaked and was cleared from the livers of muMT and wild-type mice. However, while virus was cleared from the CNS of wild-type mice, virus persisted in the CNS of muMT mice. To determine how B cells mediate viral clearance, we first assessed CD4+ T cell activation in the absence of B cells as APC. CD4+ T cells express wild-type levels of CD69 after infection in muMT mice. IFN-γ production in response to viral Ag in muMT mice was also normal during acute infection, but was decreased 31 days postinfection compared with that in wild-type mice. The role of Ab in viral clearance was also assessed. In wild-type mice plasma cells appeared in the CNS around the time that virus is cleared. The muMT mice that received A59-specific Ab had decreased virus, while mice with B cells deficient in Ab secretion did not clear virus from the CNS. Viral persistence was not detected in FcR or complement knockout mice. These data suggest that clearance of infectious mouse hepatitis virus strain A59 from the CNS requires Ab production and perhaps B cell support of T cells; however, virus is cleared from the liver without the involvement of Abs or B cells.

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Regulation of t cell responses during central nervous system viral infection

Cited by 28 publications

References 58 publications

T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody

T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody

Phenotype and Regulation of Persistent Intracerebral T Cells in Murine Toxoplasma Encephalitis

Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

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