title: Early T cell unresponsiveness in mice with candidiasis and reversal by IL-2: effect on T helper cell development.
abstract: To investigate the role and effect of IL-2 in the genesis of Th1 and Th2 responses to Candida albicans in vivo, we assessed the levels of IL-2 production and the Ag-specific proliferative response in mice with healing or nonhealing infection and the effects of IL-2 neutralization or administration on the course and outcome of infection and on the type of CD4+ Th immunity elicited. High levels of IL-2 production and Ag-specific proliferation in vitro correlated with disease progression in susceptible mice. In contrast, resolution of infection in resistant mice was accompanied by the induction of Ag-specific hyporesponsiveness and impaired IL-2 production. Progression of infection did not occur in susceptible mice treated with anti-IL-2 or anti-IL-2R mAbs; conversely, disease resolution was prevented in resistant mice treated with IL-2. CD4+ Th1 cell responses were present in BALB/c mice rendered resistant by IL-2 neutralization and CD4+ Th2 responses in mice rendered susceptible by IL-2 treatment. The presence of IL-2 restored Ag-specific responsiveness in vitro and correlated in vivo with the expansion of CD4+ MEL-149(low) cells capable of producing IL-2 and IL-4 both in vitro and in vivo as observed in adult thymectomized mice. These results indicate that production of IL-2 early in infection correlates with the induction of IL-4-producing CD4+ Th2 cells, while a transient loss of T cell responsiveness, such as IL-2 production, appears to be required for CD4+ Th1 occurrence in mice with candidiasis.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Spaccapelo
authors.forename: G
authors.initials: G
authors.lastname: Del Sero
authors.forename: P
authors.initials: P
authors.lastname: Mosci
authors.forename: F
authors.initials: F
authors.lastname: Bistoni
authors.forename: L
authors.initials: L
authors.lastname: Romani
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004198:Disease Susceptibility; D000939:Epitopes / Q000502:physiology; D005260:Female; D018960:Hyaluronan Receptors; D007108:Immune Tolerance / Q000187:drug effects*; D007113:Immunity, Innate; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D019041:L-Selectin; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000187:drug effects / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D000939:Epitopes; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D019041:L-Selectin; D015847:Interleukin-4