title: Selective role for the p55 Kd TNF-alpha receptor in immune unresponsiveness induced by an acute viral encephalitis.
abstract: Brain infection by the laboratory strain challenge virus standard (CVS), a highly neurotropic strain of rabies virus, causes splenocytes to become less responsive to in vitro stimulation with ConA. CVS-induced immune unresponsiveness is less severe in mice lacking the p55 Kd TNF-alpha receptor (p55TNFR(-/-)) than in C57BL/6 mice, despite a similar invasion of the brain. Comparison of CVS infection in these two strains of mice indicated that decreased immune responsiveness is associated with: (1) an in vivo reduction of the percentages of Th1 (IL-2, IFN-gamma and TNF-alpha) but not of Th2 (IL-4) cytokine-secreting T cells; and (2) an in vivo increase of the percentages of CD25 and CD69-expressing splenocytes. In contrast, CVS-induced immune unresponsiveness is not associated with abnormal percentage of T, B, NK cells or monocytes in vivo. The reductions of the CD4/CD8 ratio and of splenocyte expression of I-A(b) during CVS infection are similar in p55TNFR(-/-) and C57BL/6 mice indicating that these two parameters are not linked to the decreased responsiveness of splenocytes. These data suggest that CVS-induced immune unresponsiveness is under the control of the p55 Kd TNF-alpha receptor. We propose that T cell activation through this receptor, in an environment of poor antigen presentation, results in a state of T cells characterized by the reduced production of IL-2, TNF-alpha and IFN-gamma in vivo, the decreased responsiveness of splenocytes to ConA stimulation in vitro and the expression of the activation markers CD25 and CD69.
authors.affiliation: Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: S
authors.initials: S
authors.lastname: Camelo
authors.forename: M
authors.initials: M
authors.lastname: Lafage
authors.forename: A
authors.initials: A
authors.lastname: Galelli
authors.forename: M
authors.initials: M
authors.lastname: Lafon
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D016516:CD4-CD8 Ratio; D003208:Concanavalin A / Q000494:pharmacology; D018792:Encephalitis, Viral / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011818:Rabies / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000737:chemistry / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003208:Concanavalin A; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens