CD8+ T cells of Tc2 phenotype mediate a GVL effect and prevent marrow rejection.
Donor T cells mediate both beneficial and detrimental immune reactions in the setting of allogeneic BMT (alloBMT). T cells mediate the GVL effect and prevent marrow rejection, but also induce GVHD. In an attempt to favorably influence the balance of these allogeneic responses, we have evaluated the effect of donor CD4+, Th1/Th2 and CD8+, Tc1/Tc2 functional T cell subsets in murine marrow transplantation models. Our studies have identified the CD8+ Tc2 population (which is a cytolytic effector secreting the type II cytokines IL-4, IL-5, and IL-10) as a subset capable of mediating the GVL effect and preventing marrow rejection with reduced GVHD. We have also shown that the Tc2 subset can be generated in humans. These studies indicate that administration of donor CD8+ T cells of Tc2 phenotype represents a strategy for improving allo BMT outcome.
National Cancer Institute, Department of Experimental Transplantation and Immunology, Bethesda, MD 20892, USA. dhfowler@helix.nih.gov
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Fowler
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Gress
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008212:Lymphocyte Depletion; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D010641:Phenotype; D011828:Radiation Chimera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D015848:Interleukin-5; D008222:Lymphokines; D016753:Interleukin-10; D015847:Interleukin-4