Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia
Aurélie Trenado, … , Benoît L. Salomon, José L. Cohen
Aurélie Trenado, … , Benoît L. Salomon, José L. Cohen
Published December 1, 2003
Citation Information: J Clin Invest. 2003;112(11):1688-1696. https://doi.org/10.1172/JCI17702.
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Categories: Article Immunology

Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia

Abstract

CD4+CD25+ regulatory T cells (Treg’s) play a pivotal role in preventing organ-specific autoimmune diseases and in inducing tolerance to allogeneic organ transplants. We and others recently demonstrated that high numbers of Treg’s can also modulate graft-versus-host disease (GVHD) if administered in conjunction with allogeneic hematopoietic stem cell transplantation in mice. In a clinical setting, it would be impossible to obtain enough freshly purified Treg’s from a single donor to have a therapeutic effect. Thus, we performed regulatory T cell expansion ex vivo by stimulation with allogeneic APCs, which has the additional effect of producing alloantigen-specific regulatory T cells. Here we show that regulatory T cells specific for recipient-type alloantigens control GVHD while favoring immune reconstitution. Irrelevant regulatory T cells only mediate a partial protection from GVHD. Preferential survival of specific regulatory T cells, but not of irrelevant regulatory T cells, was observed in grafted animals. Additionally, the use of specific regulatory T cells was compatible with some form of graft-versus-tumor activity. These data suggest that recipient-type specific Treg’s could be preferentially used in the control of GVHD in future clinical trials.

Authors

Aurélie Trenado, Frédéric Charlotte, Sylvain Fisson, Micael Yagello, David Klatzmann, Benoît L. Salomon, José L. Cohen

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Figure 5

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GVL/GVT effects after control of GVHD by sTreg’s. (a) A20 leukemic cells...
GVL/GVT effects after control of GVHD by sTreg’s. (a) A20 leukemic cells were injected into irradiated mice at time of BMT. Results are presented as a Kaplan-Meier survival curve for mice receiving BM cells alone (dashed line, open squares, n = 5), BM cells supplemented with 0.5 × 106 conventional T cells (open circles, n = 5), in addition to 0.5 × 106 sTreg’s (filled squares, n = 5). P < 0.05 between the last two groups. GVL effect is also evaluated by the presence of A20 cells in the blood of mice detected by the coexpression of B220 and H-2Kd Ag, and also by their large size. (b) A similar experiment was reproduced using P815 cells. Results are presented as a Kaplan-Meier survival curve for mice receiving BM cells alone (dashed line, open squares, n = 5), or BM cells supplemented with 10 × 106 conventional T cells (open circles, n = 5), in addition to 10 × 106 sTreg’s (filled squares, n = 5). Because of severe morbidity due to the presence of tumor in all mice of the experimental group, the experiment was stopped at day 35.