Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia.
In allogeneic hemopoietic stem cell transplantation, mature donor alphabeta 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-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).
Zheng
Hong
H
Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Matte-Martone
Catherine
C
Jain
Dhanpat
D
McNiff
Jennifer
J
Shlomchik
Warren D
WD
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*