Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease.
We previously showed that transplantation with IL-21R gene-deficient splenocytes resulted in less severe graft-versus-host disease (GVHD) than was observed with wild type splenocytes. In this study, we 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 MLR and cytokine production by CD4(+) T cells were impaired. These results suggest that IL-21 might promote GVHD through enhanced production of effector CD4(+) T cells. Moreover, we found that CD25 depletion altered neither the impaired MLR 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.
Oh
Iekuni
I
Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Ozaki
Katsutoshi
K
Meguro
Akiko
A
Hatanaka
Keiko
K
Kadowaki
Masanori
M
Matsu
Haruko
H
Tatara
Raine
R
Sato
Kazuya
K
Iwakura
Yoichiro
Y
Nakae
Susumu
S
Sudo
Katsuko
K
Teshima
Takanori
T
Leonard
Warren J
WJ
Ozawa
Keiya
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D017353:Gene Deletion; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000502:physiology; D053738:Interleukin-21 Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D000098546:Interleukin-21
C508118:Il21r protein, mouse; D018836:Inflammation Mediators; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D000098546:Interleukin-21