title: Acute graft-versus-host reaction can be aborted by blockade of costimulatory molecules.
abstract: Injection of parental lymphocytes into an unirradiated adult F1 host results in an acute GVH reaction characterized by immune deficiency, attack on host lymphohematopoietic tissues, and repopulation with donor-derived cells. All of these events result from the initial activation of donor lymphocytes by host alloantigens. Interaction of pairs of host and donor costimulatory molecules, in particular CD28/CTLA4 and B7-1/B7-2, play a crucial role in this initial activation of donor T cells. We demonstrate here that in vivo treatment of the host with high doses of CTLA4-Ig solely during the initial period of donor alloactivation can completely abort the subsequent development of GVH reaction. Although donor T cells are retained, CTLA4-Ig treatment reduces the initial endogenous cytokine production and arrests the subsequent expansion of donor T cells, the differentiation of anti-host effectors, and the development of severe immune deficiency. This result is consistent with the establishment of host-specific tolerance in the donor population, while maintaining host immune competence.
authors.affiliation: Transplantation Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Hakim
authors.forename: R
authors.initials: R
authors.lastname: Cepeda
authors.forename: G S
authors.initials: GS
authors.lastname: Gray
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: R
authors.initials: R
authors.lastname: Abe
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D060908:CTLA-4 Antigen; D006087:Graft vs Host Reaction; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D000069594:Abatacept