In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis

被引:62
作者
Ufret-Vincenty, RL
Quigley, L
Tresser, N
Pak, SH
Gado, A
Hausmann, S
Wucherpfennig, KW
Brocke, S
机构
[1] NINDS, Neurol Dis Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA
[2] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA
[3] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA
[4] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
autoimmunity; cross-reactivity; experimental autoimmune encephalomyelitis; molecular mimicry; antigenic peptide;
D O I
10.1084/jem.188.9.1725
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Ban virus (EBV). These low dose viral peptide-specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.
引用
收藏
页码:1725 / 1738
页数:14
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