PERIPHERAL T-CELL ACTIVATION AND DELETION INDUCED BY TRANSFER OF LYMPHOCYTE SUBSETS EXPRESSING ENDOGENOUS OR EXOGENOUS MOUSE MAMMARY-TUMOR VIRUS

Murine T cell reactivity with products of the minor lymphocyte stimula tory (Mls) locus correlates with the expression of particular variable (V) domains of the T cell receptor (TCR) beta chain. It was recently demonstrated that Mls antigens are encoded by an open reading frame (O RF) in the 3' long terminal repeat of either endogenous or exogenous m ouse mammary tumor virus (MMTV). Immature thymocytes expressing reacti ve TCR-V(beta) domains are clonally deleted upon exposure to endogenou s Mtv's. Mature T cells proliferate vigorously in response to Mls-1a ( Mtv-7) in vivo, but induction of specific anergy and deletion after ex posure to Mtv-7-expressing cells in the periphery has also been descri bed. We show here that B cells and CD8+ (but not CD4+) T cells from Mt v-7+ mice efficiently induce peripheral deletion of reactive T cells u pon transfer to Mtv-7- recipients, whereas only B cells stimulate spec ific T cell proliferation in vivo. In contrast to endogenous Mtv-7, tr ansfer of B, CD4+, or CD8+ lymphocyte subsets from mice maternally inf ected with MMTV(SW), an infectious homologue of Mtv-7, results in spec ific T cell deletion in the absence of a detectable proliferative resp onse. Finally, we show by secondary transfers of infected cells that e xogenous MMTV(SW) is transmitted multidirectionally between lymphocyte subsets and ultimately to the mammary gland. Collectively our data de monstrate heterogeneity in the expression and/or presentation of endog enous and exogenous MMTV ORF by lymphocyte subsets and emphasize the l ow threshold required for induction of peripheral T cell deletion by t hese gene products.