Role of tumor necrosis factor receptors in regulating CD8 T-cell responses during acute lymphocytic choriomeningitis virus infection.
The role of tumor necrosis factor (TNF) in regulating various phases of the antiviral T-cell response is incompletely understood. Additionally, despite strong evidence ascribing a role for TNF in protecting against T-cell-dependent autoimmunity, the underlying mechanisms are still obscure. To address these issues, we have investigated the role of tumor necrosis factor receptors (TNFRs) I (p55R) and II (p75R) in regulating CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV) with wild-type, p55R-deficient (p55(-/-)), p75R-deficient (p75(-/-)), and p55R- and p75R-deficient (DKO) mice. Loss of p55R increased the number of memory CD8 T cells to only one of the two immunodominant epitopes, and p75R deficiency had a minimal impact on the T-cell response to LCMV. Strikingly, deficiency of both p55R and p75R had a more dramatic effect on the LCMV-specific CD8 T-cell response; in the DKO mice, as a sequel to enhanced expansion and a reduction in contraction of CD8 T cells, there was a substantial increase in the number of memory CD8 T cells (specific to the two immunodominant epitopes). While the majority of LCMV-specific memory CD8 T cells in wild-type mice were CD62Lhi CCR7hi (central memory), a major proportion of memory CD8 T cells in DKO mice were CD62Llo CCR7hi. TNFR deficiency did not affect the proliferative renewal of memory CD8 T cells. Taken together, these data suggested that TNFRs p55R and p75R have overlapping roles in downregulating CD8 T-cell responses and establishment of immune homeostasis during an acute viral infection.
Suresh
M
M
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. sureshm@svm.vetmed.wisc.edu
Singh
Anju
A
Fischer
Christopher
C
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000502:physiology*
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II