Acute graft-versus-host reaction can be aborted by blockade of costimulatory molecules
| Autor: | F T Hakim, R Cepeda, G S Gray, C H June, R Abe |
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| Rok vydání: | 1995 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 155:1757-1766 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.155.4.1757 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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