Role for CTLA-4 but not CD25+ T cells during Schistosoma mansoni infection of mice.
Schistosoma mansoni infection of mice increases the frequency of cells that are CD4+ CD25+ in the acute (4 and 8 weeks) and chronic (16 week) stages of infection. Depletion of > 85% of CD25+ cells in the acute or chronic stages of schistosome infection caused no overt changes in morbidity or immunological responses. The absence of effect in mice with CD25+ cells depleted may be due to the preferential expression of IL-4 and IL-10, two cytokines that are protective in schistosome infection, on CD25- CD4+ cells. We also assessed infection-induced changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4+ cells. We identified a marked expansion of CTLA-4+ population on CD25- CD4+ cells in acute and chronic infection. Blocking of CTLA-4 during acute, but not chronic infection, caused significant weight loss and altered the type 2 cytokine response of mice, with increased IL-4 and IL-5 production associated with significantly more Th2 cells and eosinophils in the liver granuloma. This study illustrates the complexity of regulation of T cells in schistosome infection and highlights a specific role for CTLA-4+, but not CD25+ cells, in the regulation of Th2 responses in helminth infection.
Walsh
C M
CM
Institute of Molecular Medicine, Trinity College Dublin, St James's Hospital, Dublin 8, Ireland.
Smith
P
P
Fallon
P G
PG
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008103:Liver Cirrhosis / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit