Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation Journal Article


Authors: Hubbard, V. M.; Eng, J. M.; Ramirez-Montagut, T.; Tjoe, K. H.; Muriglan, S. J.; Kochman, A. A.; Terwey, T. H.; Willis, L. M.; Schiro, R.; Heller, G.; Murphy, G. F.; Liu, C.; Alpdogan, O.; van den Brink, M. R. M.
Article Title: Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation
Abstract: Inducible costimulator (ICOS) is expressed on activated and memory T cells and is involved in the regulation of cytokine production. We studied the role of ICOS on alloreactive T cells in graft versus host disease (GVHD) and determined that ICOS expression was up-regulated on alloreactive T cells in recipients of an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with GVHD. We compared ICOS -/- T cells with wild-type (WT) T cells in 2 GVHD models. In both models, recipients of ICOS -/- T cells demonstrated significantly less GVHD morbidity and mortality, which was associated with less intestinal and hepatic GVHD but increased cutaneous GVHD. In addition, recipients of ICOS -/- donor T cells displayed a slight decrease in graft versus leukemia (GVL) activity. Further analysis of alloreactive ICOS -/- T cells showed no defect in activation, proliferation, cytotoxicity, and target organ infiltration. Recipients of ICOS -/- T cells had decreased serum levels of interferon-γ (IFN-γ), while interleukin-4 (IL-4) and IL-10 levels were increased, suggesting that alloreactive ICOS -/- T cells are skewed toward T helper-2 (Th2) differentiation. These data suggest a novel role for ICOS in the regulation of Th1/Th2 development of activated T cells. In conclusion, alloreactive ICOS -/- donor T cells induce less GVHD due to a Th2 immune deviation while GVL activity is slightly diminished. © 2005 by The American Society of Hematology.
Keywords: controlled study; unclassified drug; mortality; nonhuman; comparative study; protein function; antigen expression; cell proliferation; lymphocyte proliferation; t lymphocyte; t-lymphocytes; protein blood level; animal cell; mouse; animals; mice; animal tissue; cell infiltration; morbidity; interleukin 10; interleukin 4; cell line; animal experiment; animal model; hematopoietic stem cell transplantation; cell differentiation; cytotoxicity; wild type; th2 cell; lymphocyte activation; statistical significance; gamma interferon; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; upregulation; up-regulation; graft vs host disease; graft versus leukemia effect; t lymphocyte activation; alloimmunity; th2 cells; recipient; antigens, differentiation, t-lymphocyte; inducible costimulator; target organ; lymphocyte antigen
Journal Title: Blood
Volume: 106
Issue: 9
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2005-11-01
Start Page: 3285
End Page: 3292
Language: English
DOI: 10.1182/blood-2005-01-0410
PUBMED: 15956289
PROVIDER: scopus
PMCID: PMC1895338
DOI/URL:
Notes: --- - "Cited By (since 1996): 23" - "Export Date: 24 October 2012" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Glenn Heller
    325 Heller
  2. Raffaella Schiro
    4 Schiro
  3. Theis Helge Terwey
    17 Terwey
  4. Adam Kochman
    45 Kochman
  5. Vanessa Marie Hubbard
    42 Hubbard
  6. Lucy Willis
    27 Willis
  7. Jeffrey Eng
    36 Eng
  8. Kartono H Tjoe
    10 Tjoe