Effects of immunization with Cryptococcus neoformans cells or cryptococcal culture filtrate antigen on direct anticryptococcal activities of murine T lymphocytes

Muth, Sabine; Murphy, Juneann W.

doi:10.1128/iai.63.5.1645-1651.1995

Cited by 17 publications

(15 citation statements)

References 26 publications

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“…Immunization with C. neoformans. An anticryptococcal CMI response was induced in mice as previous described (35). Briefly, mice were injected with 0.1 ml of SPSS containing 10 7 heat-killed C. neoformans cells subcutaneously at two sites on the abdomen of the mice.…”

Section: Methodsmentioning

confidence: 99%

Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Muth

Murphy

1995

Infect Immun

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Assessment of the direct anticryptococcal activity of murine lymphocytes from both Cryptococcus neoformansimmunized and control mice was the focus of this investigation. We demonstrate that at a 2:1 effector cell-to-cryptococcal target cell ratio, effector cell populations comprised of ␣␤ T-cell receptor-positive T lymphocytes (98 to 99% CD3 ؉) from C. neoformans-immunized mice inhibited the growth of cryptococcal cells better than similar populations of lymphocytes from nonimmunized control mice. Almost immediately after mixing of cryptococci with the effector cells, C. neoformans-lymphocyte conjugates were observed. The percentage of conjugates increased over the first 30 min of incubation and then remained constant over the next 1.5 h. T-lymphocyte-enriched populations from C. neoformans-immunized mice formed significantly greater percentages of conjugates with cryptococci than control T lymphocytes at each time period that assessment was made. For growth inhibition to occur, direct contact between the effector and target cells was necessary, as evidenced by abrogation of cryptococcal growth inhibition when lymphocyte and cryptococcal cell populations were separated by a porous membrane during the growth inhibition assay. Vital staining of cryptococci after incubation with the T-cell-enriched populations showed that the T lymphocytes killed the cryptococcal cells.

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Section: Methodsmentioning

confidence: 99%

Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Muth

Murphy

1995

Infect Immun

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“…An immune response to C. neoformans can be induced in mice by injecting heat‐killed yeast or cryptococcal filtrate antigen (CneF) with Freund's complete adjuvant 17. Immunization with heat‐killed cryptococci has produced variable degrees of protection depending on the method of delivery 18, 19. Immunization with CneF produces a cell‐mediated response that protects mice from subsequent C. neoformans challenge, which is associated with elevated numbers of CD4 + T cells 20, 21.…”

Section: Introductionmentioning

confidence: 99%

Stimulation via Toll‐like receptor 9 reduces Cryptococcus neoformans‐induced pulmonary inflammation in an IL‐12‐dependent manner

et al. 2004

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Cytosine‐phosphate‐guanosine‐containing oligodeoxynucleotides (CpG ODN) are important vaccine adjuvants that promote Th1‐type immune responses. Cryptococcus neoformans is a serious human pathogen that replicates in the lung but may disseminate systemically leading to meningitis, particularly in immunocompromised individuals. Immunization of susceptible C57BL/6 mice with CpG ODN deviates the immune response from a Th2‐ toward a Th1‐type response following infection with C. neoformans. CpG also induces IL‐12, TNF, MCP‐1 and macrophage nitric oxide production. CD4+ and CD8+ T cells producing IFN‐γ increase in frequency, while those producing IL‐5 decrease. More importantly, pulmonary eosinophilia is significantly reduced, an effect that depends on IL‐12 and CD8+ T cells but not NK cells. CpG treatment also reduces the burden of C. neoformans in the lung, an effect that is IL‐12‐, NK cell‐ and T cell‐independent and probably reflects a direct effect of CpG on pathogen opsonization or an enhancement of macrophage antimicrobial activity. An equivalent beneficial effect is also observed when CpG ODN treatment is delivered during established cryptococcal disease. This is the first study documenting that promotion of lung TLR9 signaling using synthetic agonists enhances host defense. Activation of innate immunity has clear therapeutic potential and may even be beneficial in patients with acquired immune deficiency.

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“…The other population is designated the T amp cell population because it amplifies the anticryptococcal DTH response when transferred to mice at the time of their immunization with CneF-CFA (13,14). Two additional T-cell populations known to be upregulated by other immunization protocols are CD8 ϩ T cells that are involved in the anticryptococcal DTH response and the unconventional (major histocompatibility complex-nonrestricted) cytotoxic T cells, which can directly kill C. neoformans (27,40). Neither of the last two T-cell populations is induced by immunization with the soluble cryptococcal antigen CneF (27,40).…”

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confidence: 99%

“…Two additional T-cell populations known to be upregulated by other immunization protocols are CD8 ϩ T cells that are involved in the anticryptococcal DTH response and the unconventional (major histocompatibility complex-nonrestricted) cytotoxic T cells, which can directly kill C. neoformans (27,40). Neither of the last two T-cell populations is induced by immunization with the soluble cryptococcal antigen CneF (27,40). When stimulated with cryptococcal antigen(s), activated CD4 ϩ T cells induced by CneF-CFA display a predominant Th1 lymphokine profile (interleukin 2 and gamma interferon [IFN-␥]), and T-cell populations containing the T amp cells produce significantly more of these two cytokines than do T-cell populations that lack T amp cells (33).…”

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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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Effects of immunization with Cryptococcus neoformans cells or cryptococcal culture filtrate antigen on direct anticryptococcal activities of murine T lymphocytes

Cited by 17 publications

References 26 publications

Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice

Stimulation via Toll‐like receptor 9 reduces Cryptococcus neoformans‐induced pulmonary inflammation in an IL‐12‐dependent manner

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

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