Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation

Gerhard C. Hildebrandt, Krystyna M. Olkiewicz, Sung Choi, Leigh A. Corrion, Shawn G. Clouthier, Chen Liu, Jonathan S. Serody, Kenneth R. Cooke

Research output: Contribution to journalArticlepeer-review

Abstract

Idiopathic pneumonia syndrome (IPS) is a major cause of mortality following allogeneic stem cell transplantation (allo-SCT). Clinical and experimental data support a role for conditioning-induced inflammation and alloreactive T-cell responses in IPS pathophysiology, but the mechanisms by which donor leukocytes are ultimately recruited to the lung are not fully understood. RANTES is a chemokine ligand that is up-regulated during inflammation and promotes the recruitment of T cells and macrophages to sites of tissue damage. Using a lethally irradiated murine SCT model (B6 → B6D2F1), we evaluated the role of donor leukocyte-derived RANTES in the development of IPS. Pulmonary mRNA and protein levels of RANTES were significantly elevated in allo-SCT recipients compared to syngeneic controls and were associated with enhanced mRNA expression of CCR5 and CCR1 and with inflammatory cell infiltration into the lung. Allo-SCT with RANTES-/- donor cells significantly decreased IPS and improved survival. Combinations of allogeneic wild-type or RANTES-/-bone marrow with wild-type or RANTES-/- T cells demonstrated that the expression of RANTES by donor T cells was critical to the development of lung injury after SCT. These data reveal that donor T cells can help regulate leukocyte recruitment to the lung after allo-SCT and provide a possible mechanism through which inflammation engendered by SCT conditioning regimens is linked to allo-specific T-cell responses during the development of IPS.

Original languageEnglish (US)
Pages (from-to)2249-2257
Number of pages9
JournalBlood
Volume105
Issue number6
DOIs
StatePublished - Mar 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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