Bovine γ globulin‐specific CD4+ T cells are retained by bovine γ‐globulin‐tolerant mice*

Abstract

Immunological tolerance is an acquired state of antigen-specific nonresponsiveness which is generally attributed to either the deletion or suppression of tolerogen-specific T helper cell clones. Unresponsiveness to xenogeneic immunoglobulins can be readily induced and has been extensively studied in order to ascertain the means by which tolerance is established and maintained. As an absence of reactivity to foreign immunoglobulin has been noted in situations where suppressor cell activity was minimized, this tolerant state has often been ascribed to clonal deletion. The present study demonstrates that bovine gamma-globulin (BGG)-tolerant mice are unable to generate humoral responses to BGG in vivo and yet harbor BGG-specific CD4+CD8- T cells which can divide and secrete interleukin 2 when stimulated in vitro. Indeed, the in vitro reactivity to BGG of these cells exceeded that of a similar population of non-immune cells. This is in direct opposition to the loss of response that would be expected if clonal deletion were operative. The presence of BGG-specific CD4+ T cells, which appear to be at least partly primed, in mice unresponsive to BGG, indicates that tolerance to BGG is likely to be dependent on unidentified immunoregulatory processes rather than clonal deletion.