Allospecific CD4+, Th1/Th2 and CD8+, Tc1/Tc2 populations in murine GVL: type I cells generate GVL and type II cells abrogate GVL.

摘要: Donor CD4+ and CD8+ T cells mediate graft-vs.-leukemia (GVL) responses in the allogeneic bone marrow transplantation (alloBMT) setting. To evaluate role of functional cell subsets mediation GVL, alloreactive donor (Th1/Th2) (Tc1/Tc2) defined cytokine phenotype were generated by vitro culture. A leukemia/transplantation model (B6 into B6C3F1; 1050 cGy host irradiation) was established using bcr/abl-transfected myeloid leukemia line, 32Dp210 (P210; H-2k). Leukemia control mice (1X10(4) P210 per recipient) died at day 12.0 post-BMT. Recipients CD4+, Th1-type or CD8+, Tc1-type populations conferred a survival advantage (death 20.7 23.5 days post-BMT, respectively). In contrast, Th2-type population did not GVL 12.3 days). Furthermore, mixing experiments demonstrated that Th2 subset abrogated both Th1- Tc1-mediated GVL. The Tc2 population, which secreted type II cytokines lysed target vitro, mediated some experiments; interestingly, magnitude Tc2-mediated inversely related to level interleukin-10 (IL-10) population. These studies therefore indicate I maximally generate I/type interactions are an important consideration for setting leukemic hosts.