Open AccessInduction of suppressive allogeneic regulatory T cells via rabbit antithymocyte polyclonal globulin during homeostatic proliferation in rat kidney transplantation
Author(s) -
ValdezOrtiz Rafael,
Bestard Oriol,
Llaudó Inés,
Franquesa Marcella,
Cerezo Gema,
Torras Joan,
HerreroFresneda Inmaculada,
CorreaRotter Ricardo,
Grinyó Josep M.
Publication year - 2015
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12448
Subject(s) - medicine , foxp3 , thymoglobulin , regulatory t cell , il 2 receptor , immunology , transplantation , homeostasis , t cell , cancer research , kidney transplantation , immune system
Summary Experimental studies have shown that rabbit antithymocyte polyclonal globulin ( ATG ) can expand human CD 4+ CD 25++ F oxp3+ cells ( T regs). We investigated the major biological effects of a self‐manufactured rabbit polyclonal anti‐rat thymoglobulin (r ATG ) in vitro , as well as its effects on different peripheral T ‐cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of r ATG ‐induced T regs in an experimental rat renal transplant model. Our results show that r ATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T ‐cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the r ATG dose used, but not of the effector memory T cells, which required significantly higher r ATG doses. After r ATG administration, we observed a significant proliferation of T regs in the peripheral blood of transplanted rats, leading to an increase in the T reg/ T effector ratio. Importantly, r ATG ‐induced T regs displayed a strong donor‐specific suppressive capacity when assessed in an antigen‐specific allogeneic co‐culture. All of these results were associated with better renal graft function in rats that received r ATG . Our study shows that r ATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post‐transplant homeostatic proliferation.