TY - JOUR

T1 - 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

AU - Andersen, C

AU - Jensen, T

AU - Nansen, A

AU - Marker, O

AU - Thomsen, A R

AU - Thomsen, Allan Randrup

N1 - 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

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 10590269

VL - 11

SP - 2035

EP - 2042

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 12

ER -