Selective role for the p55 Kd TNF-alpha receptor in immune unresponsiveness induced by an acute viral encephalitis

Brain infection by the laboratory strain challenge virus standard (CVS), a highly neurotropic strain of rabies virus, causes splenocytes to become les s responsive to in vitro stimulation with ConA. CVS-induced immune unrespon siveness is less severe in mice lacking the p55 Kd TNF-alpha receptor (p55T NFR(-/-)) than in C57BL/6 mice, despite a similar invasion of the brain. Co mparison of CVS infection in these two strains of mice indicated that decre ased 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 percentage s of CD25 and CD69-expressing splenocytes. In contrast, CVS-induced immune unresponsiveness is not associated with abnormal percentage of T, B, NK cel ls or monocytes in vivo. The reductions of the CD4/CD8 ratio and of splenoc yte expression of I-A(h) during CVS infection are similar in p55TNFR(-/-) a nd C57BL/6 mice indicating that these two parameters are not linked to the decreased responsiveness of splenocytes. These data suggest that CVS-induce d immune unresponsiveness is under the control of the p55 Kd TNF-alpha rece ptor. We propose that T cell activation through this receptor. in an enviro nment of poor antigen presentation, results in a state of T cells character ized by the reduced production of IL-2, TNF-alpha and IFN-gamma in vivo, th e decreased responsiveness of splenocytes to ConA stimulation in vitro and the expression of the activation markers CD25 and CD69. (C) 2001 Elsevier S cience B.V. All rights reserved.