Altered effector CD4+ T cell function in IL-21R−/− CD4+ T cell-mediated graft-versus-host disease1

• Published in: The Journal of immunology (1950) Vol. 185; no. 3; pp. 1920 - 1926
• Main Authors: Oh, Iekuni, Ozaki, Katsutoshi, Meguro, Akiko, Hatanaka, Keiko, Kadowaki, Masanori, Matsu, Haruko, Tatara, Raine, Sato, Kazuya, Iwakura, Yoichiro, Nakae, Susumu, Sudo, Katsuko, Teshima, Takanori, Leonard, Warren J., Ozawa, Keiya
• Format: Journal Article
• Language: English
• Published: 23.06.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902217

We previously showed that transplantation with interleukin-21 receptor (IL-21R) gene-deficient splenocytes resulted in less severe GVHD than was observed with wild type splenocytes. We now here sought to find mechanism(s) explaining this observation. Recipients of donor CD4 + T cells lacking IL-21R exhibited diminished GVHD symptoms, with reduced inflammatory cell infiltration into the liver and intestine, leading to prolonged survival. After transplantation, CD4 + T cell-numbers in the spleen were reduced and mixed lymphocyte reaction and cytokine production by CD4 + T cells were impaired. These results suggest that IL-21 might promote GVHD through enhancing production of effector CD4 + T cells. Moreover, we found that CD25 depletion altered neither the impaired mixed lymphocyte reaction in vitro nor the ameliorated GVHD symptoms in vivo. Thus, the attenuated GVHD might be caused by an impairment of effector T-cell differentiation itself rather than by an increase in regulatory T-cells and suppression of effector T-cells.