Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets.
IL-21 regulates certain functions of T cells, B cells, NK cells and dendritic cells. Although activated CD4(+) T cells produce IL-21, data identifying the specific CD4(+) T cell subsets that produce IL-21 are conflicting. In a previous study, mouse IL-21 message was detected in T(H)2, whereas human IL-21 (hIL-21) message was found in both T(H)1 and follicular helper T cells. To identify the IL-21-secreting cell populations in human, we established a hybridoma cell line producing an anti-hIL-21 mAb. Intracellular hIL-21-staining experiments showed that hIL-21 was mainly expressed in activated CD4(+) central memory T cells and in activated CD4(+) effector memory T cells, but not in activated CD4(+) naive T cells. Moreover, IL-21 was produced upon activation by some IFN-gamma-producing T(H)1-polarized cells and some IL-17-producing T(H)17-polarized cells, but not by IL-4-producing T(H)2-polarized cells. These results suggest that specific CD4(+) T cell populations produce IL-21. In the functional analysis, we found that IL-21 significantly enhanced the cytokine-driven proliferation of CD4(+) helper T cells synergistically with IL-7 and IL-15 without T cell activation stimuli. Taken together, IL-21 produced from CD4(+) memory T cells may have a supportive role in the maintenance of CD4(+) T cell subsets.
Onoda
Tadashi
T
Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Rahman
Mizanur
M
Nara
Hidetoshi
H
Araki
Akemi
A
Makabe
Koki
K
Tsumoto
Kouhei
K
Kumagai
Izumi
I
Kudo
Toshio
T
Ishii
Naoto
N
Tanaka
Nobuyuki
N
Sugamura
Kazuo
K
Hayasaka
Kiyoshi
K
Asao
Hironobu
H
D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D006825:Hybridomas; D007156:Immunologic Memory; D007378:Interleukins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D000098546:Interleukin-21
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007378:Interleukins; D000098546:Interleukin-21