Heart Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Heart Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody can prevent rat cardiac allograft rejection.

Kitazawa Y, Fujino M, Sakai T, Azuma H, Kimura H, Isaka Y, Takahara S, Hünig T, Abe R, Li XK

Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

BACKGROUND: It is well known that CD4(+)CD25(+) regulatory T (Treg) cells play a central role in the suppression of autoimmunity, inflammation and allograft rejection. Therefore, therapeutic agents that capable of enhancing the number and activity of this T-cell subset are highly desirable. METHODS: The present study was designed to investigate the effects of superagonistic CD28-specific monoclonal antibody (supCD28 MAb) on preferentially expanded rat naturally occurring CD4(+)CD25(+) Treg (nTreg) cells and its applicability in cardiac transplantation. RESULTS: A single administration of supCD28 MAb preferentially proliferated nTreg cells. The increase of Foxp3 expression and polarization toward a Th2 cytokine profile correlated with decreased production of interferon-gamma and increased production of interleukin-4 and -10 in the expanded CD4(+)CD25(+) Treg subset, which was capable of suppressing CD4(+)CD25(-) T-cell proliferation after purification. Furthermore, supCD28 MAb administration revealed that nTreg cells were preferentially proliferating in vivo and recruited into the grafts, resulting in significant prolongation of full MHC-mismatch cardiac graft survival. CONCLUSIONS: Our data demonstrate that supCD28 MAb targets expansion of nTreg cells in vivo and maintains and enhances their regulatory functions, which represents a major advance toward the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of allograft rejection.

Published 31 March 2008 in J Heart Lung Transplant, 27(4): 362-71.
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