Deletion of CD4+ T cells by mouse mammary tumor virus (FM) superantigen with broad specificity of T cell receptor beta-chain variable region.
We previously identified a superantigen from the exogenous mouse mammary tumor virus carried by FM mice [MMTV (FM)], which can preferentially activate V beta 8.2+ 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) beta-chain variable region (V beta) 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 V beta 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 exerted a protective effect on the development of EAE in (PL/J x SJL)F1 mice. Thus, MMTV (FM) superantigen has the ability to delete a large portion 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 agent against autoimmune diseases.
Yoshimoto
T
T
Department of Allergology, University of Tokyo, Japan. yoshimot@ims.u-tokyo.ac.jp
Nagase
H
H
Nakano
H
H
Matsuzawa
A
A
Nariuchi
H
H
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000821:virology; D007519:Isoantigens / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology*; D018089:Superantigens / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology*; D014611:Vaccination
D000956:Antigens, Viral; D017252:CD3 Complex; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D010047:Ovalbumin