Conservation of Pathogenic TCR Homology Across Class II Restrictions in Anti-RNP Autoimmunity: Extended Efficacy of T Cell Vaccine Therapy1

T cells have been shown to mediate aspects of anti-RNP autoimmunity, and are a potential target of therapy in lupus and related diseases. In this study, we assessed the relevance of a conserved class of anti-RNP T cells to autoimmune disease expression and therapy. Our data show that anti-RNP T cell...

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Veröffentlicht in:The Journal of immunology (1950) 2014-03, Vol.192 (9), p.4093-4102
Hauptverfasser: Zang, YunJuan, Martinez, Laisel, Fernandez, Irina, Pignac-Kobinger, Judith, Greidinger, Eric L.
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Sprache:eng
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Zusammenfassung:T cells have been shown to mediate aspects of anti-RNP autoimmunity, and are a potential target of therapy in lupus and related diseases. In this study, we assessed the relevance of a conserved class of anti-RNP T cells to autoimmune disease expression and therapy. Our data show that anti-RNP T cell selection induced a limited set of homologous CDR3 motifs at high frequency. Homologous CDR3 motifs have been reported in other autoimmune diseases. Vaccination with irradiated anti-RNP (but not anti-Tetanus Toxoid) CD4+ cells induced remission of anti-RNP-associated nephritis in at least 80% of treated mice, even with donor/recipient MHC Class II mismatch, and in both induced and spontaneous autoimmunity. Vaccine responder sera inhibited anti-70k T cell proliferation and bound hybridomas expressing the conserved CDR3 motifs. Our data indicate that a limited set of TCR CDR3 motifs may be important for the pathogenesis of anti-RNP lupus and other autoimmune diseases. The ability to target a consistent set of pathogenic T cells between individuals and across Class II restrictions may allow for the more practical development of a standardized anti-RNP T cell vaccine preparation useful for multiple patients.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1203197