Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia

In allogeneic hemopoietic stem cell transplantation, mature donor alpha beta T cells in the allograft promote T cell reconstitution in the recipient and mediate the graft-vs-leukemia (GVL) effect. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-vs-host disease (GVHD). It has previously been shown that effector memory T cells not primed to alloantigen do not cause GVHD yet transfer functional T cell memory and mediate GVL. Recently, central memory T cells (T-CM) have also been reported to not cause GVHD. In contrast, in this study, we demonstrate that purified CD8(+) T-CM not specifically primed to alloantigens mediate GVHD in the MHC-mismatched C57BL/6 (B6)-> BALB/c and the MHC-matched, multiple minor histocompatibility Ag-mismatched C3H center dot SW -> B6 strain pairings. CD8(+) T-CM and naive T cells (T-N) caused similar histological disease in liver, skin, and bowel. B6 CD8(+) T-CM and T-N similarly expanded in BALB/c recipients, and the majority of their progeny produced IFN-gamma upon restimulation. However, in both models, CD8(+) T-CM induced milder clinical GVHD than did CD8(+) T-N. Nonetheless, CD8(+) T-CM and T-N were similarly potent mediators of GVL against a mouse model of chronic-phase chronic myelogenous leukemia. Thus, in contrast to what was previously thought, CD8(+) T-CM are capable of inducing GVHD and are substantially different from T-EM but only subtly so from T-N. The Journal of Immunology, 2009, 182: 5938-5948.