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.
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.
Authors: Steven L Rosinski; Rainer Storb; Roland K Strong; George E Sale; Diane M Stone; Mesfin M Gewe; Della J Friend; V Kraig Abrams; Julie Randolph-Habecker; Scott S Graves Journal: Transplant Direct Date: 2015-03
Authors: Daniela Langenhorst; Paula Tabares; Tobias Gulde; Bryan R Becklund; Susanne Berr; Charles D Surh; Niklas Beyersdorf; Thomas Hünig Journal: Front Immunol Date: 2018-01-30 Impact factor: 7.561
Authors: Tea Gogishvili; Daniela Langenhorst; Fred Lühder; Fernando Elias; Karin Elflein; Kevin M Dennehy; Ralf Gold; Thomas Hünig Journal: PLoS One Date: 2009-02-27 Impact factor: 3.240