CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation

Sung W. Choi, Gerhard C. Hildebrandt, Krystyna M. Olkiewicz, David A. Hanauer, Meghana N. Chaudhary, Ines A. Silva, Clare E. Rogers, Daphne T. Deurloo, Jacki M. Fisher, Chen Liu, David Adams, Stephen W. Chensue, Kenneth R. Cooke

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Acute graft-versus-host disease (GVHD) and leukemic relapse are serious complications of allogeneic stem-cell transplantation (SCT). Recruitment of activated T cells to host target tissues or sites of leukemic infiltration (graft-versus-leukemia [GVL]) is likely mediated by chemokine receptor-ligand interactions. We examined the contribution of donor cell CCR1 expression to the development of GVHD and GVL using a well-established murine SCT model (B6 → B6D2F1) and CCR1-deficient mice (CCR1-/-). Allo-SCT with CCR1 -/- donor cells significantly reduced systemic and target organ GVHD severity, and CCR1 expression on both T cells and accessory cells contributed to GVHD mortality. Significant GVL activity was preserved following CCR1 -/- SCT, but the survival advantage diminished with increasing tumor burden. We then explored the effects of CCR1 expression on allo-specific T-cell responses. Although cytolytic effector function was maintained on a per-cell basis, T-cell proliferation and IFNγ secretion were significantly reduced both in vivo and in vitro. T-cell function was partially dependent on interactions between CCR1 and CCL5. Collectively, these data demonstrate that CCR1 expression on donor cells contributes to the development of both GVHD and GVL, and suggest that CCR1/CCL5 receptor ligand interactions modulate allo-specific T-cell responses occurring in this context.

Original languageEnglish
Pages (from-to)3447-3455
Number of pages9
JournalBlood
Volume110
Issue number9
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint

Dive into the research topics of 'CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation'. Together they form a unique fingerprint.

Cite this