A crucial role for host APCs in the induction of donor CD4 +CD25+ regulatory T cell-mediated suppression of experimental graft-versus-host disease

Isao Tawara, Warren D. Shlomchik, Angela Jones, Weiping Zou, Evelyn Nieves, Chen Liu, Tomomi Toubai, Raimon Duran-Struuck, Yaping Sun, Shawn G. Clouthier, Rebecca Evers, Kathleen P. Lowler, Robert B. Levy, Pavan Reddy

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Allogeneic bone marrow transplantation is an effective treatment for a number of malignant and nonmalignant diseases (Applebaum. 2001. Nature. 411:385-389 and Copelan. 2006. N Engl J Med. 354:1813-1826). However, the application of this therapeutic modality has been impeded by a number of confounding side effects, the most frequent and severe of which is the development of graft-versushost disease (GVHD) (Copelan. 2006. N Engl J Med. 354:1813-1826 and Blazar and Murphy. 2005. Philos Trans R Soc Lond B Biol Sci. 360:1747-1767). Alloreactive donor T cells are critical for causing GVHD (Fowler. 2006. Crit Rev Oncol Hematol. 57:225-244 and Ferrara and Reddy. 2006. Semin Hematol. 43:3-10), whereas recent data demonstrated a significant role for the naturally occurring thymic-derived donor CD4+CD25 +Foxp3+ regulatory T cells (Tregs) (Bluestone and Abbas. 2003. Nat Rev Immunol. 3:253-257 and Shevach. 2006. Immunity. 25:195-201) in suppressing experimental GVHD after bone marrow transplantation (Blazar and Taylor. 2005. Biol Blood Marrow Transpl. 11:46-49 and Joffe and van Meerwijk. 2006. Semin Immunol. 18:128-135). Host APCs are required for induction of GVHD by the conventional donor T cells. However, it is not known whether they are also obligatory for donor Tregmediated suppression of GVHD. Using multiple clinically relevant MHC-matched and-mismatched murine models of GVHD, we investigated the role of host APCs in the suppression of GVHD by donor Tregs. We found that alloantigen expression by the host APCs is necessary and sufficient for induction of GVHD protection by donor Tregs. This requirement was independent of their effect on the maintenance of Treg numbers and the production of IL-10 or IDO by the host APCs.

Original languageEnglish (US)
Pages (from-to)3866-3872
Number of pages7
JournalJournal of Immunology
Volume185
Issue number7
DOIs
StatePublished - Oct 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tawara, I., Shlomchik, W. D., Jones, A., Zou, W., Nieves, E., Liu, C., Toubai, T., Duran-Struuck, R., Sun, Y., Clouthier, S. G., Evers, R., Lowler, K. P., Levy, R. B., & Reddy, P. (2010). A crucial role for host APCs in the induction of donor CD4 +CD25+ regulatory T cell-mediated suppression of experimental graft-versus-host disease. Journal of Immunology, 185(7), 3866-3872. https://doi.org/10.4049/jimmunol.1001625