Deletion of CD4+T Cells by Mouse Mammary Tumor Virus (FM) Superantigen with Broad Specificity of T Cell Receptor β-Chain Variable Region

Abstract

We previously identified a superantigen from the exogenous mouse mammary tumor virus carried by FM mice [MMTV (FM)], which can preferentially activate Vβ8.2+CD4+T cells by subcutaneous injection. In the present study we investigated the effect of neonatal infection with the virus on the T cell receptor (TCR) β-chain variable region (Vβ) repertoire, T cell immune response, and development of experimental allergic encephalomyelitis (EAE). The infection, surprisingly, resulted in deletion of a large portion of CD4+T cells including Vβ2+, 6+, 8.1+, 8.3+, and 14+CD4+T cells in addition to Vβ8.2+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-Vβ8.2 antibody-mediated receptor cross-linking. Moreover, the infection exerted a protective effect on the development of EAE in (PL/J × SJL)F1 mice. Thus, MMTV (FM) superantigen has the ability to delete a large portion of CD4+T cells with broad TCR Vβ specificity, including Vβ8.2+CD4+T cells, and may have potential as a therapeutic agent against autoimmune diseases.