Abstract
Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired resistance of mice to challenge with virulent Candida albicans, and release macrophage-activating cytokines in response to yeast cells in vitro. To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2. Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were used as target cells in a standard 51Cr release assay. Ag-specific, MHC-unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells after 5–10 days in culture. Under the same experimental conditions, the cytotoxic activity of L3T4+ cells was negligible, but its expression could be induced by the addition of anti-CD3 antibody.
Culturing immune Lyt-2+ cells for shorter periods of time (1–2 days) resulted in preferential lysis of infected neutrophils. In addition, at limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity to infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic T-cell precursors with varying recognition stringency, wich may have an important role in antifungal resistance in vivo.
Similar content being viewed by others
References
AshmanR.B. and PapadimitriouJ.M. (1990): What's new in the mechanisms of host resistance to Candida albicans infection? - Path. Res. Pract. 186: 527–534.
BistoniF., YecchiarelliA., CenciE., PuccettiP., MarconiP. and CassoneA. (1986): Evidence for macrophage-mediated protection against lethal C. albicans infection - Infect. Immun. 51: 668–674.
BodeyG.P. and AnaissieE.J. (1989): Chronic systemic candidiasis - Eur. J. Clin. Microbiol. Infect. Dis. 8: 855–857.
CantornaM.T. and BalishE. (1990): Mucosal and systemic candididasis in congenitally immunodeficient mice - Infect. Immun. 58: 1093–1100.
CenciE., RomaniL., YecchiarelliA., PuccettiP. and BistoniF. (1989): Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice - Infect. Immun. 57: 3581–3587.
CenciE., RomaniL., YecchiarelliA., PuccettiP, and BistoniF. (1990): T-cell subsets and IFN-γ production in resistance to systemic candidosis in immunized mice - J. Immunol. 144: 4333–4339.
ChiplunkarS., DeLiberoG. and KaufmannS.H.E. (1986): Mycobacterium leprae-specific Lyt-2+ T lymphocytes with cytolytic activity - Infect. Immun. 54: 793–797.
DeLiberoG., FleshI. and KaufmannA.H.E. (1988): Mycobacteria-reactive Lyt-2+ T cell lines - Eur. J. Immunol. 18: 59–66.
DeLiberoG. and KaufmannS.H.E. (1986): Antigen-specific Lyt-2+ cytolytic T lymphocytes from mice infected with the intracellular bacterium Listeria monocytogenes - J. Immunol. 137: 2688–2694.
DjeuJ.Y., BlanchardD.K., RichardsA.L. and FriedmanH. (1988): Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes - J. Immunol. 141: 4047–4052.
DomerJ.E. (1988): Intragastric colonization of infant mice with Candida albicans induces systemic immunity demonstrable upon challenge as adults - J. Infect. Dis. 157: 950–958.
GrohmannU., UllrichS.J., MageM.G., AppellaE., FiorettiM.C., PuccettiP. and RomaniL. (1990): Identification and immunogenic properties of an 80-kDa surface antigen on a drug-treated tumor variant: relationship to MuLV gp70 - Eur. J. Immunol. 20: 629–636.
JackR.M. and FearonD. T. (1988): Selective synthesis of mRNA and proteins by human peripheral blood neutrophils - J. Immunol. 140: 4286–4293.
KaufmannS.H.E. (1988): CD8+ T lymphocytes in intracellular microbial infections - Immunol. Today 9: 168–174.
KaufmannS.H.E. (1991): Role of T-cell subsets in bacterial infections - Cuff. Opin. Immunol. 3: 465–470.
KaufmannS.H.E., HugE. and DeLiberoG. (1986): Listeria monoctogenes-reactive T lymphocyte clones with cytolytic activity against infected target cells - J. Exp. Med. 164: 363–368.
KaufmannS.H.E., RodewaldH.-R., HugE. and DeLiberoG. (1988): Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity - J. Immunol. 140: 3173–3179.
KleinR.S., HarrisC.A., SmallC.B., MollB., LesserM. and FriedlandG.H. (1984): Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome - N. Eng. J. Med. 311: 354–358.
LinehanL., WadsworthE. and CalderoneR. (1986): Candida albicans C3d receptor, isolated by using a monoclonal antibody - Infect. Immun. 56: 1981–1986.
LukacsK. and KurlanderR. (1989): Lyt-2+ T cell-mediated protection against listeriosis. Protection correlates with phagocyte depletion but not with IFN-γ production - J. Immunol. 142: 2879–2886.
LukacsK. and KurlanderR. (1989): MHC-restricted transfer of antilisterial immunity by freshly isolated immune CD8 spleen cells - J. Immunol. 143: 3731–3736.
MielkeM.E.A., EhlersS. and HahnH. (1988): T-cell subsets in DTH, protection and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity - Immunol. Lett. 19: 211–216.
MiyakeT., TakeyaK., NomotoK. and MuraokaJ. (1977): Cellular elements in the resistance to Candida infection in mice. I. Contribution of T lymphocytes and phagocytes at various stages of infection -Microbiol. Immunol. 21: 703–725.
MorrisonW.I., GoddeerisB.M., TealeA.J., BaldwinC.L., BensaidA. and EllisJ. (1986): Cell-mediated immune responses of cattle to Theileria parva -Immunol. Today 7: 211–216.
MosmannT.R. and CoffmanR.L. (1989): Heterogeneity of cytokine secretion patterns and functions of helper T cells - Adv. Immunol. 46: 111–147.
MüllerI., CobboldS.P., WaldmannH. and KaufmannS.H.E. (1987): Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells - Infect. Immun. 55: 2037–2041.
OddsF.C. (1988): Candida and candidosis. 2and ed. Ballière Tindall, London.
PetersonP.K., LeeD.SuhH.J., DevalonM., NelsonR.D. and KeaneW F. (1986): Intracellular survival of Candida albicans in peritoneal macrophages from chronic peritoneal dialysis patients - Am. J. Kidney Dis. 7: 146–152.
RollwagenF.M., DaschG.A. and JerrelsT.R. (1986): Mechanisms of immunity to rickettsial infection: characterization of a cytotoxic effector cell - J. Immunol. 136: 1418–1421.
RomaniL., MocciS., BiettaC., LanfaloniL., PuccettiP. and BistoniF. (1991): Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance - Infect. Immun. 59: 4647–4654.
RomaniL., MocciS., CenciE., RossiR., PuccettiP. and BistoniF. (1991): Candida albicans-specific Lyt-2+ lymphocytes with cytolytic activity - Eur. J. Immunol. 21: 1567–1570.
RutheR.C., AndersonB.R, CunninghamB.L. and EsteinR.B. (1978): Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host - Blood 52: 493–498.
ShortmanK., WilsonA., ScollayR. and ChenW. (1983): Development of large granular lymphocytes with anomalous, nonspecific cytotoxicity in clones derived from Lyt-2+ cells - Proc. Natl. Acad. Sci. USA 80: 2728–2732.
VecchiarelliA., CenciE., PulitiM., BlasiE., PuccettiP., CassoneA. and BistoniF. (1989): Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state - Cell. Immunol. 124: 334–344.
WiltonJ.M.A. and LehenerT. (1980): Immunology of candidiasis - Comprehensive Immunol. 8: 525–559.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Romani, L., Mocci, S., Cenci, E. et al. Antigen-specific cytolysis of infected cells in murine candidiasis. Eur J Epidemiol 8, 368–376 (1992). https://doi.org/10.1007/BF00158570
Issue Date:
DOI: https://doi.org/10.1007/BF00158570