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18250226
Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro.

Blood, 2008/4/01;111(7):3675-83.

Feng X[1], Kajigaya S, Solomou EE, Keyvanfar K, Xu X, Raghavachari N, Munson PJ, Herndon TM, Chen J, Young NS

Affiliations

PMID: 18250226DOI: 10.1182/blood-2008-01-130146

Impact factor: 25.476

Abstract
Regulatory T cells (Treg) play important roles in suppressing immune responses and maintaining tolerance. Rabbit antithymocyte globulin (rATG) and horse ATG (hATG) are widely used in the treatment of immune-mediated syndromes, but their effects on Treg are unknown. We show here that in vitro culture of normal human peripheral blood mononuclear cells (PBMCs) with a low-dose rATG resulted in marked expansion of functional Treg by converting CD4+CD25- T cells to CD4+CD25+ T cells. hATG did not expand but rather decreased Treg. Immuno-blot showed increased expression of FOXP3 and NFAT1 in CD4+CD25- and CD4+CD25+ T cells exposed to rATG. PBMCs treated with rATG displayed increased interleukin-10 in culture supernatants than those treated with hATG. Furthermore, rATG and hATG showed differences in their potential to stimulate CD4+ T cells as examined using different activation markers. Microarray revealed that rATG induced markedly different gene-expression patterns in PBMCs, compared with hATG-treated or untreated PBMCs. Our findings indicate that rATG expanded Treg, probably through transcriptional regulation by enhanced NFAT1 expression, in turn conferring CD4+CD25- T cell FOXP3 expression and regulatory activity. The therapeutic effects of rATG may occur not only because of lymphocyte depletion but also enhanced Treg cell number and function.
MeSH terms
Animals; Antilymphocyte Serum; Cell Culture Techniques; Cell Proliferation; Cells, Cultured; Forkhead Transcription Factors; Gene Expression Profiling; Gene Expression Regulation; Horses; Humans; Immune System Diseases; Immune Tolerance; Immunosuppressive Agents; Interleukin-10; NFATC Transcription Factors; Oligonucleotide Array Sequence Analysis; Rabbits; Species Specificity; Syndrome; T-Lymphocytes, Regulatory
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