Mutant HSP70i prevents effector T cell responses in autoimmune vitiligo (P4352)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.177-177.9
• Main Authors: Mosenson, Jeffrey, Zloza, Andrew, Nieland, John, Garrett-Mayer, Elizabeth, Eby, Jonathan, Huelsmann, Erica, Kumar, Previn, Denman, Cecele, Lacek, Andrew, Kohlhapp, Frederick, Alamiri, Ahmad, Hughes, Tasha, Bines, Steven, Kaufman, Howard, Overbeck, Andreas, Mehrotra, Shikhar, Hernandez, Claudia, Nishimura, Michael, Guevara-Patino, Jose, Le Poole, I. Caroline
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.177.9

A single amino acid change (Q435A) within HSP70i renders an isoform with treatment potential for vitiligo, as demonstrated by ablated depigmentation in gene gun vaccinated, vitiligo-prone TCR transgenic mice. We hypothesized that HSP70iQ435A inhibits T cell mediated immune responses. We probed skin from gene gun vaccinated P-mel1 and h3TA2 mice for T cell infiltrates and analyzed splenocytes for T cell activation markers by FACS, comparing findings to those in tissues from vitiligo patients and among cells collected from human skin explants exposed to HSP70iQ435A. Decreased skin infiltration was observed for T cells responsible for melanocyte killing in both mouse strains. Eomes/T-bet ratios were significantly decreased by wild-type HSP70i driving an effector phenotype, whereas vaccination with HSP70iQ435A maintains a quiescent phenotype. This ratio was similarly decreased in circulating and skin-infiltrating T cells from vitiligo patients where we also observed an increase in CXCR3 expression, supportive of skin homing. In cells from skin explants exposed to wild-type or mutant HSP70i the Eomes/T-bet ratio is upregulated by HSP70iQ435A whereas upregulation of skin homing receptor CLA followed exposure to wildtype HSP70. In conclusion, the wild-type HSP70i-induced T cell effector phenotype accompanied by elevated CXCR3 and CLA expression observed in vitiligo is countered by HSP70iQ435A exposure, providing a mechanism for HSP70iQ435A induced inhibition of autoimmunity.