Critical role for CCR5 in the function of donor CD4+CD25 + regulatory T cells during acute graft-versus-host disease

Christian A. Wysocki, Qi Jiang, Angela Panoskaltsis-Mortari, Patricia A. Taylor, Karen P. McKinnon, Lishan Su, Bruce R. Blazar, Jonathan S. Serody

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

CD4+CD25+ regulatory T cells (Tregs) have been shown to inhibit graft-versus-host disease (GVHD) in murine models, and this suppression was mediated by Tregs expressing the lymphoid homing molecule L-selectin. Here, we demonstrate that Tregs lacking expression of the chemokine receptor CCR5 were far less effective in preventing lethality from GVHD. Survival of irradiated recipient animals given transplants supplemented with CCR5-/- Tregs was significantly decreased, and GVHD scores were enhanced compared with animals receiving wild-type (WT) Tregs. CCR5-/- Tregs were functional in suppressing T-cell proliferation in vitro and ex vivo. However, although the accumulation of Tregs within lymphoid tissues during the first week after transplantation was not dependent on CCR5, the lack of function of CCR5-/- Tregs correlated with impaired accumulation of these cells in the liver, lung, spleen, and mesenteric lymph node, more than one week after transplantation. These data are the first to definitively demonstrate a requirement for CCR5 in Treg function, and indicate that in addition to their previously defined role in inhibiting effector T-cell expansion in lymphoid tissues during GVHD, later recruitment of Tregs to both lymphoid tissues and GVHD target organs is important in their ability to prolong survival after allogeneic bone marrow transplantation.

Original languageEnglish (US)
Pages (from-to)3300-3307
Number of pages8
JournalBlood
Volume106
Issue number9
DOIs
StatePublished - Nov 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Critical role for CCR5 in the function of donor CD4<sup>+</sup>CD25 <sup>+</sup> regulatory T cells during acute graft-versus-host disease'. Together they form a unique fingerprint.

  • Cite this

    Wysocki, C. A., Jiang, Q., Panoskaltsis-Mortari, A., Taylor, P. A., McKinnon, K. P., Su, L., Blazar, B. R., & Serody, J. S. (2005). Critical role for CCR5 in the function of donor CD4+CD25 + regulatory T cells during acute graft-versus-host disease. Blood, 106(9), 3300-3307. https://doi.org/10.1182/blood-2005-04-1632