Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia

H Zheng, C Matte-Martone, D Jain, J McNiff… - The Journal of …, 2009 - journals.aai.org
H Zheng, C Matte-Martone, D Jain, J McNiff, WD Shlomchik
The Journal of Immunology, 2009journals.aai.org
In allogeneic hemopoietic stem cell transplantation, mature donor αβ 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 …
Abstract
In allogeneic hemopoietic stem cell transplantation, mature donor αβ 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. 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-γ 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.
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