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

Hong Zheng, Catherine Matte-Martone, Dhanpat Jain, Jennifer McNiff, Warren D. Shlomchik

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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 (TCM) have also been reported to not cause GVHD. In contrast, in this study, we demonstrate that purified CD8+ TCM 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+ TCM and naive T cells (TN) caused similar histological disease in liver, skin, and bowel. B6 CD8+ T CM and TN similarly expanded in BALB/c recipients, and the majority of their progeny produced IFN-γ upon restimulation. However, in both models, CD8+ TCM induced milder clinical GVHD than did CD8+ TN. Nonetheless, CD8+ TCM and TN 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+ TCM are capable of inducing GVHD and are substantially different from TEM but only subtly so from TN.

Original languageEnglish (US)
Pages (from-to)5938-5948
Number of pages11
JournalJournal of Immunology
Volume182
Issue number10
DOIs
StatePublished - May 15 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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