The cellular basis of cardiac allograft rejection. IX. Ratio of naïve CD4+CD25+ T cells/CD4+CD25- T cells determines rejection or tolerance

Transplant Immunology
Masaru NomuraBruce M Hall

Abstract

Naïve CD4+ T cells are central to allograft rejection, but include 3-10% CD4+CD25+ T cells that induce and maintain immune tolerance. Whether increasing the ratio of CD4+CD25+ T cells can inhibit rejection and induce tolerance is not known. This study examined the effects that naïve CD4+CD25+ and CD4+CD25- T cells have on rejection of MHC incompatible PVG cardiac allografts in whole body irradiated DA rats. The ratio of CD4+CD25+ T cells to CD4+CD25- T cells was increased to examine if this delayed rejection. CD4+CD25- T cells alone restored near first set rejection time of 8-10 days and were significantly faster than unfractionated CD4+ T cells which nearly always took over 10 days to effect rejection. Enriched CD4+CD25+ T cells, either fresh or cultured with IL-2 and donor alloantigen, did not restore rejection. Admixing naïve CD4+CD25+ T cells with CD4+ T cells at a ratio of 1:10 prevented graft destruction by rejection. Naïve CD4+CD25+ T cells, either fresh or cultured with IL-2 and donor alloantigen, at a ratio of 1:1, prevented significant episodes of rejection and grafts survived >300 days. These grafts had large areas of normal myocardium but had some foci of CD4+, CD8+ and CD25+ cellular infiltration. This study found ...Continue Reading

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Citations

Jun 23, 2012·PloS One·Hugh I McFarlandAmy S Rosenberg
Jul 15, 2015·Journal of Evidence-based Complementary & Alternative Medicine·Mansur IbrahimSutiman B Sumitro
Oct 23, 2012·Cellular & Molecular Immunology·Hongtao LiuGuihua Hou
Apr 17, 2015·Clinical Journal of the American Society of Nephrology : CJASN·Bruce M Hall
Jan 9, 2017·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Hongtu Zhang
Jan 15, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·G XiaJ R Leventhal
Apr 8, 2020·Cardiology Research and Practice·Jie ChenLihua Duan
Sep 8, 2017·Frontiers in Immunology·Bruce M HallSuzanne J Hodgkinson

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