DELETION OF CD4(-CELLS BY MOUSE MAMMARY-TUMOR VIRUS (FM) SUPERANTIGENWITH BROAD-SPECIFICITY OF T-CELL RECEPTOR BETA-CHAIN VARIABLE REGION() T)

We previously identified a superantigen from the exogenous mouse mamma ry tumor virus carried by FM mice [MMTV (FM)], which can preferentiall y activate V beta 8.2(+) CD4(+) T cells by subcutaneous injection. In the present study we investigated the effect of neonatal infection wit h the virus on the T cell receptor (TCR) beta-chain variable region (V beta) repertoire, T cell immune response, and development of experime ntal allergic encephalomyelitis (EAE). The infection, surprisingly, re sulted in deletion of a large portion of CD4(+) T cells including V be ta 2(+), 6(+), 8.1(+), 8.3(+), and 14(+) CD4(+) T cells in addition to V beta 8.2(+) CD4(+) T cells. Nevertheless, the infection marginally affected T cell immune response to various antigens such as ovalbumin (OVA) and alloantigen except the abrogated response to anti-V beta 8.2 antibody-mediated receptor cross-linking. Moreover, the infection exe rted a protective effect on the development of EAE in (PL/J x SJL)F1 m ice. Thus, MMTV (FM) superantigen has the ability to delete a large po rtion of CD4(+) T cells with broad TCR V beta specificity, including V beta 8.2(+) CD4(+) T cells, and may have potential as a therapeutic a gent against autoimmune diseases. (C) 1996 Academic Press, Inc.