Interleukin-2 inhibits polarization to T helper type 1 cells and prevents mouse acute graft-versus-host disease through up-regulating suppressors of cytokine signalling-3 expression of naive CD4+ T cells.
T helper type 1 (Th1)-type polarization plays a critical role in the pathophysiology of acute graft-versus-host disease (aGVHD). The differentiation of T cells into this subtype is dictated by the nature of the donor naive CD4(+) T cell-host antigen presenting cell (APC) interaction. Suppressors of cytokine signalling (SOCS) are a family of molecules that act as negative regulators for cytokine signalling, which regulate the negative cytokine signalling pathway through inhibiting the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules are essential for T cell development and differentiation. SOCS-3 can inhibit polarization to Th1 and contribute to polarization to Th2. In this study, we found that interleukin (IL)-2 pre-incubation of C57BL/6 naive CD4(+) T cells could up-regulate the expression of SOCS-3. Naive CD4(+) T cells constitutively expressed low levels of SOCS-3 mRNA. SOCS-3 mRNA began to rise after 4 h, and reached peak level at 6 h. At 8 h it began to decrease. High expression of SOCS-3 mRNA induced by IL-2 could inhibit the proliferation of naive CD4(+) T cells following stimulation with allogeneic antigen. IL-2-induced high SOCS-3 expression in naive CD4(+) T cells could inhibit polarization to Th1 with stimulation of allogeneic antigens. We have demonstrated that IL-2-induced high SOCS-3 expression in naive CD4(+) T cells could reduce the incidence of aGVHD between major histocompatibility complex (MHC) completely mismatched donor and host when high SOCS3 expression of CD4(+)T cells encounter allogeneic antigen in time. These results show that IL-2-induced high SOCS-3 expression can inhibit aGVHD through inhibiting proliferation and polarization to Th1 with the stimulation of allogeneic antigen.
Zhao
J
J
Department of Haematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Zhang
T
T
He
H
H
Xie
Y
Y
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D053612:Janus Kinases / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D050791:STAT Transcription Factors / Q000276:immunology / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000970:Antineoplastic Agents; D007376:Interleukin-2; D007519:Isoantigens; D012333:RNA, Messenger; D050791:STAT Transcription Factors; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases