Memory CD4+ T cells do not induce graft-versus-host disease
Britt E. Anderson, … , Mark J. Shlomchik, Warren D. Shlomchik
Britt E. Anderson, … , Mark J. Shlomchik, Warren D. Shlomchik
Published July 1, 2003
Citation Information: J Clin Invest. 2003;112(1):101-108. https://doi.org/10.1172/JCI17601.
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Article Immunology

Memory CD4+ T cells do not induce graft-versus-host disease

Abstract

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell–mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L–CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L–CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

Authors

Britt E. Anderson, Jennifer McNiff, Jun Yan, Hester Doyle, Mark Mamula, Mark J. Shlomchik, Warren D. Shlomchik

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CD25 expression on naive and memory CD4 subsets. B10.D2 spleen cells enr...
CD25 expression on naive and memory CD4 subsets. B10.D2 spleen cells enriched for CD4 cells as described in Methods were stained with mAb’s against CD4, CD25, CD62L, and CD44. We found that 12.4% of CD4 cells were CD25+ (a). We gated on CD62L+CD44– naive and CD62L–CD44+ memory CD4 cells (b) and analyzed their expression of CD25 (c and d). Note that 33.1% of cells with a memory phenotype express CD25 versus 5.1% of cells with a naive phenotype.