Factors involved in peripheral T cell tolerance: the extent of clonal deletion or clonal anergy depends on the age of the tolerized lymphocytes

Abstract

After injection of SEB (staphylococcus enterotoxin B), normal adult mice, or thymectomized irradiated mice (TX irr.) reconstituted with lymphocytes taken from normal adult mice became specifically tolerant of SEB. At the same time the percentage of V {38 positive CD4 lymphocytes known to be responsive to SEB was almost 50% decreased, indicating that a high level of clonal deletion was realized. In contrast, mice with an exclusively old T cell compartment (old thymectomized mice, TX irr. mice reconstituted several months previously) became tolerant of SEB without deleting their V {38 + CD4 + cells, indicating that clonal anergy was the major mechanism in play in the induction of tolerance. Finally, TX irr. mice reconstituted with single positive thymocytes known to become recent thymic emigrants developed tolerance for SEB together with a high level (70%) of clonal deletion. Altogether these results indicated that the mechanism involved in peripheral tolerance depended on the age of the lymphocyte: very young lymphocytes underwent mainly clonal deletion whereas long lived lymphocytes underwent predominantly clonal anergy.

Increased Mortality and Impaired Clonal Deletion After Staphylococcal Enterotoxin B Injection in Old Mice: Relation to Cytokines and Nitric Oxide Production

“…Previously, we have demonstrated that in irradiated mice reconstituted with T cells the extent of deletion after SEB injection was determined by the age of the reconstituting lymphocytes [36]. Also other publications showed that T cells from aged mice were resistant to SEB-induced deletion [7].…”

“…In vivo NO synthesis has been shown to have a protective effect on SEB-induced shock syndrome, possibly by down-regulating IFN-g and TNF production [36]. In order to find out whether differences in cytokines might also be related to differences in the production of NO, we analyzed nitrate þ nitrite levels in plasma of SEB-injected old and young mice.…”