CD4(+) T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4
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To investigate the mechanism(s) whereby T cells protect against a lethal outcome of systemic infection with vesicular stomatitis virus, mice with targeted defects in genes central to T cell function were tested for resistance to i.v. infection with this virus. Our results show that mice lacking the capacity to secrete both IFN-gamma and perforin completely resisted disease. Similar results were obtained using IL-4 knockout mice, indicating that neither cell-mediated nor T(h)2-dependent effector systems were required. In contrast, mice deficient in expression of CD40 ligand were more susceptible than wild-type mice, and residual resistance in these mice was almost completely abrogated by depletion of CD8(+) T cells. In keeping with this, mice lacking both MHC class I and class II expression succumbed to the infection, whereas most class II-deficient mice normally survive. Adoptive transfer experiments using B cell- and T cell-deficient recipients revealed that no protection could be obtained in the absence of B cells, whereas treatment with virus-specific immune (IgG) serum controlled viral spreading to the central nervous system (CNS), but did not necessarily accomplish virus elimination. Taken together, these results underscore that B cells are essential in preventing early infection of the CNS, but T cells are required for long-term survival. CD4(+) T cells are most efficient in this context and the key function is to provide cognate help to B cells. However, if CD4(+) cell function is compromised, CD8(+) T cells become critical and may suffice for survival.
Original language | English |
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Journal | International Immunology |
Volume | 11 |
Issue number | 12 |
Pages (from-to) | 2035-42 |
Number of pages | 7 |
ISSN | 0953-8178 |
Publication status | Published - 1999 |
Bibliographical note
Keywords: Animals; Antibodies, Viral; Antigens, CD8; CD4-Positive T-Lymphocytes; CD40 Ligand; Female; Immunoglobulin G; Interferon-gamma; Interleukin-4; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Nude; Rhabdoviridae Infections; Vesicular stomatitis Indiana virus
ID: 9701706