Work

Opposing effects of ICOS on graft-versus-host disease mediated by CD4 and CD8 T cells

Year: 2006

Type: article

Abstract: Inducible costimulatory molecule (ICOS), a CD28 family member expressed on activated CD4+ and CD8+ T cells, plays important roles in T cell activation and effector function. Here we studied the role of ICOS in graft-versus-host disease (GVHD) mediated by CD4+ or CD8+ T cells in allogeneic bone marrow transplantation (BMT). In comparison of wild type (WT) and ICOS-deficient T cells, we found that recipients of ICOS−/− CD4+ T cells exhibited significantly less GVHD morbidity and mortality. ICOS−/− CD4+ T cells had no defect in expansion, but expressed significantly less FasL and produced significantly lower levels of IFN-γ and TNF-α. Thus, ICOS−/− CD4+ T cells were impaired in effector functions that lead to GVHD. In contrast, recipients of ICOS−/− CD8+ T cells exhibited significantly enhanced GVHD morbidity and mortality. In the absence of ICOS signaling, either using ICOS-deficient donors or ICOS-ligand deficient recipients, the levels of expansion and Tc1 cytokine production of CD8+ T cells were significantly increased. The level of expansion was inversely correlated with the level ofapoptosis, suggesting that increased ability of ICOS−/− CD8+ T cells to induce GVHD was resulted from the enhanced survival and expansion of those cells. Our findings indicate that ICOS has paradoxical effects on the regulation of alloreactive CD4+ and CD8+ T cells in GVHD.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2005.11.179

Authors: X.-Z. Yu, Y. Liang, N.I. Roza, C. Anasetti, C. Dong

Institutions: Moffitt Cancer Center, The University of Texas MD Anderson Cancer Center

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,650