Unique roles of Schistosoma japonicum protein Sj16 to induce IFN-γ and IL-10 producing CD4(+)CD25(+) regulatory T cells in vitro and in vivo.
Various proteins are expressed during different stages of schistosome development that are essential for cercarial penetration of vertebrate skin and evasion of host immune response. CD4(+)CD25(+) regulatory T cells are important in modulating immune responses towards helminth infections. Schistosoma japonicum protein Sj16 present in the secretions of schistosomula has been shown to have anti-inflammatory effects; however, it is uncertain whether Sj16 can induce CD4(+)CD25(+) regulatory T cells to participate in the regulation of early infection. In this study, we demonstrate a relationship between recombinant Sj16 (rSj16) and the induction of CD4(+)CD25(+) Foxp3(+) regulatory T cells. An increase in CD4(+)CD25(+) T cells was observed both in splenic cells from mice injected with rSj16 and the cells pretreated with rSj16, respectively. The induced CD4(+)CD25(+) T cells suppressed CD4(+)CD25(-) T-cell proliferation; furthermore, IFN-γ and IL-10 released from rSj16-stimulated cells contribute to this suppression. Additionally, rSj16-treated bone marrow dendritic cells (BMDCs) demonstrate an immature phenotype and play a role in the conversion of CD4(+)CD25(-) T cells into suppressive CD4(+)CD25(+) regulatory T cells. Our study identified a new CD4(+)CD25(+) T-cell population that induced by rSj16 and suggests that an IFN-γ-biased microenvironment during early infection of schistosome may favour the establishment of infection.
Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.
X J
XJ
Sun
R
R
Li
X
X
Sun
Y
Y
Zhou
Y
Y
Wang
X J
XJ
Liu
Q
Q
Lu
C L
CL
Zhou
Z D
ZD
Wu
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D015801:Helminth Proteins / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012549:Schistosoma japonicum / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
D000947:Antigens, Helminth; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007371:Interferon-gamma