@article {542926,
	title = {Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells.},
	journal = {J Immunol},
	volume = {162},
	number = {11},
	year = {1999},
	month = {1999 Jun 1},
	pages = {6368-77},
	abstract = {Blockade with B7 antagonists interferes with CD28:B7 and CTLA-4:B7 interactions, which may have opposing effects. We have examined the roles of CD28:B7 and CTLA-4:B7 on in vivo alloresponses. A critical role of B7:CD28 was demonstrated by markedly compromised expansion of CD28-deficient T cells and diminished graft-versus-host disease lethality of limited numbers of purified CD4+ or CD8+ T cells. When high numbers of T cells were infused, the requirement for CD28:B7 interaction was lessened. In lethally irradiated recipients, anti-CTLA-4 mAb enhanced in vivo donor T cell expansion, but did not affect, on a per cell basis, anti-host proliferative or CTL responses of donor T cells. Graft-versus-host lethality was accelerated by anti-CTLA-4 mAb infusion given early post-bone marrow transplantation (BMT), mostly in a CD28-dependent fashion. Donor T cells obtained from anti-CTLA-4 mAb-treated recipients were skewed toward a Th2 phenotype. Enhanced T cell expansion in mAb-treated recipients was strikingly advantageous in the graft-versus-leukemia effects of delayed donor lymphocyte infusion. In two different systems, anti-CTLA-4 mAb enhanced the rejection of allogeneic T cell-depleted marrow infused into sublethally irradiated recipients. We conclude that blockade of the selective CD28-B7 interactions early post-BMT, which preserve CTLA-4:B7 interactions, would be preferable to blocking both pathways. For later post-BMT, the selective blockade of CTLA-4:B7 interactions provides a potent and previously unidentified means for augmenting the GVL effect of delayed donor lymphocyte infusion.},
	keywords = {Animals, Antibodies, Blocking, Antibodies, Monoclonal, Antigens, CD, Antigens, CD28, Antigens, CD80, Antigens, Differentiation, Bone Marrow Transplantation, CTLA-4 Antigen, Graft Rejection, Graft vs Host Disease, Graft vs Tumor Effect, Histocompatibility Antigens, Immunoconjugates, Lymphocyte Transfusion, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Postoperative Period, Signal Transduction, Spleen, T-Lymphocytes},
	issn = {0022-1767},
	author = {Blazar, B R and Taylor, P A and Panoskaltsis-Mortari, A and Sharpe, A. H. and Vallera, D A}
}
