Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3[LATIN CAPITAL LETTER OPEN E] humanized mice treated with polyclonal anti human thymocyte globulin

• Published in: PloS one 2017-03, Vol.12 (3)
• Main Authors: Buszko, Maja, Cardini, Benno, Oberhuber, Rupert, Oberhuber, Lukas, Jakic, Bojana, Beierfuss, Anja, Wick, Georg, Cappellano, Giuseppe
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0173088

Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3[LATIN CAPITAL LETTER OPEN E] transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points. We found a significant T cell depletion in this mouse model. In addition, regulatory T cells (Tregs) proved to be less sensitive to depletion than the rest of T cells and the Treg:non-Treg ratio was therefore increased. Finally, we also investigated the effect of ATG in a heterotopic allogenic murine model of heart transplantation. Survival and transplant function were significantly prolonged in ATG-treated mice. In conclusion, we showed (a) an immunosuppressive effect of ATG in this humanized mouse model which is exclusively mediated by reactivity against human CD3[LATIN CAPITAL LETTER OPEN E]; (b) provided evidence for a relative resistance of Tregs against this regimen; and (c) demonstrated the immunomodulatory effect of ATG under these experimental circumstances by prolongation of heart allograft survival.