200
Pharmacological Research, Vol . 26, Supplement 2, 1992
IMMUNOREGULATORY ROLE OF DIFFERENT T CELL SUBSETS IN MURINE CANDIDIASIS L . ROMANI, S . MOCCI, E . CENCI, A . MENCACCI, P . MOSCI and F . BISTONI Department of Experimental Medicine and Biochemical Sciences, Microbiology sect ., University of Perugia, Perugia, Italy Key words : CD4+/CD8+ cells, immunoregulation, candidiasis Specific anti-Candida immunity can be induced in mice by vaccination with a low-virulence Candida variant strain (1) . We have previously shown that T cells and/or their soluble products crucially participate in the expression of acquired immunity to Candida albicans infection (2,3) . To establish whether T cells and/or T-cell derived cytokines also participate during the early stages of infection in the generation of protective immunity, CD2F1 mice depleted of CD4+ and/or CD8+ T lymphocytes were injected with 10 cells of a low-virulence C . albicans strain . Depletion was obtained by injection of monoclonal antibodies (0 .5 mg/mouse, i .p .) directed to either one of the two surface antigens, 2 days before vaccination and weekly thereafter for 3 weeks . Resistance was evaluated by injection of the animals with a lethal dose of C . albicans 14 days after vaccination . Results of mortality data showed that mice depleted of the CD4+ population did not develop protective immunity in that all mice succumbed . On the contrary, mice depleted of CD8+ T cells survived challenge, thus pointing to a minor role of the CD8+ lymphocytes in generation of anticandidal immunity . Spleen cells from antibody-treated mice were analyzed for their ability to release cytokines in vitro in response to specific antigen . It was found that CD8+-depleted mice produced higher amounts of IFN-IS than CD4+-depleted, early in the course of infection . Table I IFN-is production by splenocytes from antibody-treated mice Treatment in vivoa)
IFN-2j
None Mab a CD4 Mab a CD8
41 b) 8 37
a) Spleen cells were taken 3 days after vaccination with lowvirulence Candida cells and cultured for 72 h in vitro with heat-inactivated Candida cells before collection of supernatants . b) IFN-' activity (U/ml) was measured as protection of mouse L929 cells from the cytopathic effect of vesicular stomatitis virus, as previously described (3) .
1043-6618/92/26110200-02/$03 .00/0
© 1992 The Italian Pharmacological Society
Pharmacological Research, Vol. 26, Supplement 2, 1992
Taken together, these results show that T cells and/or their soluble products also regulated the generation of acquired immunity to C . albicans cells . In particular, an early production of IFN-2(, possibly mediated by CD4+ cells, seems to be a crucial event in determining generation of anticandidal resistance in a mouse model of systemic infection . Acknowledgements This study was supported by Progetto Finalizzato FATMA, contract no . 91 .00088 .PF41, from the Consiglio Nazionale delle Ricerche, Italy . References 1 . Cenci E, Romani L, Vecchiarelli A, Puccetti P, Bistoni F . Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice . Infect Immun 1989 ; 57 : 3581-7 . 2 . Cenci E, Romani L, Vecchiarelli A, Puccetti P, Bistoni F . T cell subsets and IFN-W production in resistance to systemic candidosis in immunized mice . J Immunol 1990 ; 144 : 4333-9 . 3 . Vecchiarelli A, Mazzolla R, Farinelli S, Cassone A, Bistoni F . Immunomodulation by Candida albicans : crucial role of organ colonization and chronic infection with an attenuated agerminative strain of C . albicans for establishment of anti-infectious protection . J Gen Microbiol 1988 ; 134 : 2583-92 .
20 1
Pharmacological Research, Vol . 26, Supplement 2, 1992
IMMUNOREGULATORY ROLE OF DIFFERENT T CELL SUBSETS IN MURINE CANDIDIASIS L . ROMANI, S . MOCCI, E . CENCI, A . MENCACCI, P . MOSCI and F . BISTONI Department of Experimental Medicine and Biochemical Sciences, Microbiology sect ., University of Perugia, Perugia, Italy Key words : CD4+/CD8+ cells, immunoregulation, candidiasis Specific anti-Candida immunity can be induced in mice by vaccination with a low-virulence Candida variant strain (1) . We have previously shown that T cells and/or their soluble products crucially participate in the expression of acquired immunity to Candida albicans infection (2,3) . To establish whether T cells and/or T-cell derived cytokines also participate during the early stages of infection in the generation of protective immunity, CD2F1 mice depleted of CD4+ and/or CD8+ T lymphocytes were injected with 10 cells of a low-virulence C . albicans strain . Depletion was obtained by injection of monoclonal antibodies (0 .5 mg/mouse, i .p .) directed to either one of the two surface antigens, 2 days before vaccination and weekly thereafter for 3 weeks . Resistance was evaluated by injection of the animals with a lethal dose of C . albicans 14 days after vaccination . Results of mortality data showed that mice depleted of the CD4+ population did not develop protective immunity in that all mice succumbed . On the contrary, mice depleted of CD8+ T cells survived challenge, thus pointing to a minor role of the CD8+ lymphocytes in generation of anticandidal immunity . Spleen cells from antibody-treated mice were analyzed for their ability to release cytokines in vitro in response to specific antigen . It was found that CD8+-depleted mice produced higher amounts of IFN-IS than CD4+-depleted, early in the course of infection . Table I IFN-is production by splenocytes from antibody-treated mice Treatment in vivoa)
IFN-2j
None Mab a CD4 Mab a CD8
41 b) 8 37
a) Spleen cells were taken 3 days after vaccination with lowvirulence Candida cells and cultured for 72 h in vitro with heat-inactivated Candida cells before collection of supernatants . b) IFN-' activity (U/ml) was measured as protection of mouse L929 cells from the cytopathic effect of vesicular stomatitis virus, as previously described (3) .
1043-6618/92/26110200-02/$03 .00/0
© 1992 The Italian Pharmacological Society
Pharmacological Research, Vol. 26, Supplement 2, 1992
Taken together, these results show that T cells and/or their soluble products also regulated the generation of acquired immunity to C . albicans cells . In particular, an early production of IFN-2(, possibly mediated by CD4+ cells, seems to be a crucial event in determining generation of anticandidal resistance in a mouse model of systemic infection . Acknowledgements This study was supported by Progetto Finalizzato FATMA, contract no . 91 .00088 .PF41, from the Consiglio Nazionale delle Ricerche, Italy . References 1 . Cenci E, Romani L, Vecchiarelli A, Puccetti P, Bistoni F . Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice . Infect Immun 1989 ; 57 : 3581-7 . 2 . Cenci E, Romani L, Vecchiarelli A, Puccetti P, Bistoni F . T cell subsets and IFN-W production in resistance to systemic candidosis in immunized mice . J Immunol 1990 ; 144 : 4333-9 . 3 . Vecchiarelli A, Mazzolla R, Farinelli S, Cassone A, Bistoni F . Immunomodulation by Candida albicans : crucial role of organ colonization and chronic infection with an attenuated agerminative strain of C . albicans for establishment of anti-infectious protection . J Gen Microbiol 1988 ; 134 : 2583-92 .
20 1
