Superagonistic CD28 stimulation of allogeneic T cells protects from acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD) often precludes successful immunotherapy of hematologic malignancies with allogeneic T cells. Therefore, we investigated the effect of immunomodulatory superagonistic anti-CD28 monoclonal antibodies (CD28-SA) on the capacity of allogeneic T cells to mediate both aGVHD and the protective graft-versus-tumor (GVT) response. In vivo pretreatment of donor C57BL/6 mice or short-term in vitro culture of donor lymph node cells with a CD28-SA efficiently protected BALB/c recipient mice from aGVHD. This protection strongly relied on the presence of CD28-SA-activated CD4+ CD25+ Foxp3+ regulatory T cells in the donor T-cell inoculum. With respect to the GVT response, CD28-SA-prestimulated T cells were still as potent in clearing lymphoma cells as were T cells without CD28-SA preactivation. Taken together, our data suggest that CD28-SA stimulation of bulk leukocyte cultures in vitro markedly increases the therapeutic window for adoptive immunotherapy with allogeneic T cells in vivo.
Beyersdorf
Niklas
N
University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany.
Ding
Xin
X
Hünig
Thomas
T
Kerkau
Thomas
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D018106:CD28 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens