Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Muth, Sabine; Murphy, Juneann W.

doi:10.1128/iai.63.5.1637-1644.1995

Cited by 24 publications

(14 citation statements)

References 35 publications

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“…Mice immunized with HKC with or without CFA have populations of T cells not found in the mice immunized with CneF-CFA. These are CD8 ϩ cells which contribute to anticryptococcal DTH reactivity and unconventional cytotoxic T cells that directly kill C. neoformans (27,39,40). Since HKC immunization induces little to no protection in mice, these two components do not appear to be playing a role in protection.…”

Section: Discussionmentioning

confidence: 99%

“…The organism was maintained and grown on modified Sabouraud dextrose agar. HKC for immunization were prepared by heating C. neoformans 184A cells for 1 h at 60°C (39). Viable C. neoformans cells for infection were collected from a 3-day culture, washed three times in endotoxin-free sterile physiological saline solution (SPSS), counted, and diluted to the appropriate concentration in SPSS.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast to immunization with CneF-CFA, s.c. immunization with HKC induces both CD4 ϩ and CD8 ϩ T cells, which are involved in the anticryptococcal DTH response (27). In addition, the direct anticryptococcal activity of an unconventional cytotoxic T cell is augmented by immunization with HKC either alone or in CFA (27,39,40).…”

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confidence: 99%

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Antigen-Induced Protective and Nonprotective Cell-Mediated Immune Components againstCryptococcus neoformans

et al. 1998

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Mice immunized with two different cryptococcal antigen preparations, one a soluble culture filtrate antigen (CneF) in complete Freund’s adjuvant (CFA) and the other heat-killed Cryptococcus neoformans cells (HKC), develop two different profiles of activated T cells. CneF-CFA induces CD4+ T cells responsible for delayed-type hypersensitivity (DTH) reactivity and for amplification of the anticryptococcal DTH response, whereas HKC induce CD4+ and CD8+ T cells involved in anticryptococcal DTH reactivity and activated T cells which directly kill C. neoformans cells. The main purpose of this study was to assess the level of protection afforded by each of the two different T-cell profiles against challenge with viable C. neoformans cells, thereby identifying which activated T-cell profile provides better protection. CBA/J mice immunized with CneF-CFA had significantly better protective responses, based on better clearance of C. neoformans from tissues, on longer survival times, and on fewer and smaller lesions in the brain, than HKC-immunized mice or control mice similarly infected with C. neoformans. Both immunization protocols induced an anticryptococcal DTH response, but neither induced serum antibodies to glucuronoxylmannan, so the protection observed in the CneF-CFA immunized mice was due to the activated T-cell profile induced by that protocol. HKC-immunized mice, which displayed no greater protection than controls, did not have the amplifier cells. Based on our findings, we propose that the protective anticryptococcal T cells are the CD4+ T cells which have been shown to be responsible for DTH reactivity and/or the CD4+ T cells which amplify the DTH response and which have been previously shown to produce high levels of gamma interferon and interleukin 2. Our results imply that there are protective and nonprotective cell-mediated immune responses and highlight the complexity of the immune response to C. neoformans antigens.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Antigen-Induced Protective and Nonprotective Cell-Mediated Immune Components againstCryptococcus neoformans

et al. 1998

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“…Such activity has been described against Cryptococcus neoformans and C. albicans . In mice given either live or heat-killed Cryptococcus neoformans, a population of lymphocytes developed that had direct antifungal activity in vitro, and direct contact between the fungus and lymphocytes was required (Fung & Murphy, 1982;Muth & Murphy, 1995). Human lymphocytes also have these properties, and fractionation into CD4 1 T cells, CD8 1 cells, and CD56 1 NK cells showed that each population had antifungal properties that required cellular interaction (Levitz, 1991;Levitz & Dupont, 1993;Murphy et al, 1993;Levitz et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Toxicity toCandida albicansmediated by human serum and peripheral blood mononuclear cells

Bliss

Laforce-Nesbitt

2006

FEMS Immunology &Amp; Medical Microbiology

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This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans-specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell-cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections.

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“…Reductions in GM-CSF from constitutive levels did not occur when the LGL were prevented from making contact with the C. neoformans cells. It is well established that NK and T cells must bind to C. neoformans cells to inhibit the growth of the organism (13,28,30), and so we investigated whether the LGL had to be in direct contact with the C. neoformans cells to observe the reduction in GM-CSF production. To test this, Transwell plates were used.…”

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confidence: 99%

Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production

1997

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Human natural killer (NK) cells and T lymphocytes can bind to and inhibit the growth of the yeast-like organism Cryptococcus neoformans. Binding of target cells to NK or T cells also has the potential to modulate cytokine production by the effector cells. In this study, we assessed the ability of C. neoformans to modulate NK cell production, or in some cases T-cell production, of granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor alpha (TNF-␣). We found that freshly isolated human NK cells from most individuals make GM-CSF and TNF-␣ constitutively when cultured in vitro. The addition of C. neoformans to T-cell fractions which do not make GM-CSF constitutively did not affect GM-CSF production, but the addition of C. neoformans to NK cell fractions significantly reduced the amounts of GM-CSF produced in most NK cell samples. The reduction in the amount of GM-CSF in C. neoformans-NK cell cocultures could not be attributed to loss of lymphocyte viability or to C. neoformans adsorbing or degrading the cytokine and was dependent on direct contact between the NK cells and cryptococcal cells. GM-CSF was not the only cytokine to be downregulated. TNF-␣ production was also diminished when NK cells were incubated with C. neoformans. The regulation of both cytokines was at the transcriptional level because GM-CSF and TNF-␣ mRNA levels were lower in NK cell samples incubated with C. neoformans than in NK cell samples incubated without C. neoformans. Diminished production of constitutively produced cytokines resulting from the interaction of NK cells with cryptococcal cells has the potential to affect phagocytic cells in the immediate regional environment and to damp the immune response. MATERIALS AND METHODSReagents. The reagents used in these studies were purchased from the following vendors: RPMI 1640 medium and pooled human serum (type AB) from Gibco Laboratories, Grand Island, N.Y.; fetal bovine serum (FBS) from Hy-Clone Laboratories, Inc., Logan, Utah; penicillin, streptomycin, Ficoll-Hypaque, Percoll, and phorbol myristate acetate (PMA) from Pharmacia, Uppsala, Sweden; nylon wool from Robbins Scientific Corp., Sunnyvale, CA.; fluorescein isothiocyanate-conjugated mouse anti-human CD3 monoclonal antibody (immunoglobulin G1 IgG1), phycoerythrin (PE)-conjugated mouse anti-human CD16 monoclonal antibody (IgG1), PE-conjugated mouse anti-human CD14 monoclonal antibody (IgG2), and fluorescein isothiocyanate-conjugated and PE-conju-* Corresponding author. Mailing address:

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Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Cited by 24 publications

References 35 publications

Antigen-Induced Protective and Nonprotective Cell-Mediated Immune Components againstCryptococcus neoformans

Antigen-Induced Protective and Nonprotective Cell-Mediated Immune Components againstCryptococcus neoformans

Toxicity toCandida albicansmediated by human serum and peripheral blood mononuclear cells

Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production

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