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 journalArticle

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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

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Graft vs Host Disease
Leukemia
T-Lymphocytes
Transplants
Isoantigens
Graft vs Leukemia Effect
Leukemia, Myeloid, Chronic Phase
Histocompatibility
Stem Cell Transplantation
Allografts
Liver Diseases
Skin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Zheng, Hong ; Matte-Martone, Catherine ; Jain, Dhanpat ; McNiff, Jennifer ; Shlomchik, Warren D. / Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia. In: Journal of Immunology. 2009 ; Vol. 182, No. 10. pp. 5938-5948.
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Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia. / Zheng, Hong; Matte-Martone, Catherine; Jain, Dhanpat; McNiff, Jennifer; Shlomchik, Warren D.

In: Journal of Immunology, Vol. 182, No. 10, 15.05.2009, p. 5938-5948.

Research output: Contribution to journalArticle

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AU - Matte-Martone, Catherine

AU - Jain, Dhanpat

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