title: Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice.
abstract: Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cenci
authors.forename: L
authors.initials: L
authors.lastname: Romani
authors.forename: A
authors.initials: A
authors.lastname: Vecchiarelli
authors.forename: P
authors.initials: P
authors.lastname: Puccetti
authors.forename: F
authors.initials: F
authors.lastname: Bistoni
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D008222:Lymphokines