Graft-versus-host resistance induced by class II major histocompatibility complex-specific T cell clones.

摘要: Possible mechanisms of graft-vs.-host (GVH) resistance have been studied using a panel seven class II major histocompatibility complex-specific T cell clones for elicitation and challenge. One clone recognized I-Ak,d,f, expressed V beta 8.3 together with J 1.5. The remaining six were I-Ek specific 15 rearranged to 1.1 or 1.3. I-Ek-specific also homologous each other different from the I-A-reactive one in D N regions. Four exhibited cytolytic activity. Each clone, when injected sublethal numbers into appropriate recipients, could induce subsequent lethal dose any panel. did not require sharing either receptor chains antigen specificity, MHC molecules by eliciting challenging clone. Cytolytic noncytolytic equally efficient inducing GVH resistance. A prerequisite induction was activation recognition host. Clones preactivated high concentrations recombinant interleukin 2, vitro, syngeneic hosts, suggesting that associated activated state rather than per se. In all instances resistance, failed vascular leakage, which cause death susceptible recipients (Lehmann, P. V., G. Schumm, D. Moon, U. Hurtenbach, F. Falcioni, S. Muller, Z. A. Nagy. 1990. J. Exp. Med. 171:1485). Lipopolysaccharide (LPS) induced leakage provide crossresistance vice versa, 1 alpha tumor necrosis factor implicated LPS are involved Although mechanism remains unclear, most likely explanation this system is downregulation permeability increasing effect an refractoriness blood vessels effect.