Regulation of cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response

Buchanan, Kent L.; Murphy, Juneann W.

doi:10.1128/iai.62.7.2930-2939.1994

Cited by 39 publications

(12 citation statements)

References 25 publications

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“…In the present study, we assessed the abilities of these two immunization protocols, which induce different cellular components, to protect mice from infection with C. neoformans. After finding that CneF-CFA immunization afforded a significant level of protection, whereas HKC immunization did not, we analyzed the ability of the HKC immunization to induce T amp cells, which are responsible for augmented IFN-␥ production (5,33). We found that HKC immunization did not induce T amp cells, suggesting that T amp cells may be important in the mechanism of clearance of C. neoformans.…”

mentioning

confidence: 97%

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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confidence: 97%

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

et al. 1998

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“…For fungal models, few data are available to implicate a particular cytokine in a specific inhibitory phenomenon. Buchanan and Murphy (7), however, reported decreased quantities of IL-2 and IFN-␥ in antigen-soaked sponges implanted in animals given cryptococcal antigen-specific suppressor-inducer (Ts1) cells, but whether the decreased production of these two cytokines resulted from the lack of stimulation of T cells involved in the normal DH response or from a more direct effect of a third factor and/or cell downregulating the production of the two cytokines is unknown. IL-5 was detected in the sponges as well, but there were no differences between those from immune and downregulated mice.…”

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confidence: 99%

Alterations in Frequency of Interleukin-2 (IL-2)-, Gamma Interferon-, or IL-4-Secreting Splenocytes Induced byCandida albicansMannan and/or Monophosphoryl Lipid A

Domer

1998

Infect Immun

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We have shown previously that intravenous injection ofCandida albicans mannan (MAN) into naive mice induced CD8+ effector downregulatory cells and that such cells were not produced if mice were deficient in CD4+ or I-A+ cells during the early interval (≤30 h) following the introduction of MAN. Moreover, the nonspecific biological response modifier monophosphoryl lipid A (MPL), given in vivo or incubated with cells in vitro, can abrogate the MAN-specific immunomodulatory activity. The mechanism by which the abrogation is mediated is unknown, but it is hypothesized to involve cytokines. Therefore, we measured the number of cytokine-secreting cells for the Th1 cytokine interleukin-2 (IL-2) and the Th2 cytokine IL-4, as well as for gamma interferon (IFN-γ), in splenocyte populations from MAN and/or MPL-treated mice, using an enzyme-linked immunospot assay designed to detect individual cytokine-secreting cells (spot-forming cells [SFC]). Cytokine-secreting cells were demonstrated in cell suspensions enriched for CD4+ cells, but no SFC could be demonstrated in populations enriched for CD8+ cells. Both MAN and MPL, when administered to separate groups of animals, stimulated the production of increased numbers of cytokine-producing cells for each of the three cytokines tested. The response with respect to IL-4-secreting cells, however, was the most striking. Despite the fact that MAN and MPL independently caused increases in SFC to all three cytokines, when both MAN and MPL were administered to the same animal, all increases were reversed, and the numbers of SFC detected were at or below those detected in saline control animals. These data support the hypothesis that IL-4 is involved in MAN-specific immunoregulatory activities. The data also emphasize the fact that two immunomodulators, i.e., MAN and MPL, having similar effects when given in vivo independently, may be antagonistic when administered sequentially to the same animal.

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“…IFN-␥ message was not upregulated during the induction phase of suppression in the MAN-specific model, i.e., Յ48 h after the injection of MAN, but it was thereafter. Finally, Buchanan and Murphy (7) reported increased production of IL-5 in suppressed mice, with decreased production of IFN-␥ and IL-2. IL-4 was unchanged.…”

Section: Discussionmentioning

confidence: 94%

“…The administration of exogenous IL-12 prevented the induction of immune suppression by UV and also prevented the activity of preformed suppressor cells (61). In one of the few fungal models in which cytokine involvement in downregulation has been studied, increased secretion of IL-5 and decreased secretion of IFN-␥ and IL-2 were detected (7).…”

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confidence: 99%

Cytokine Involvement in Immunomodulatory Activity Affected byCandida albicansMannan

Wang

Moser

et al. 1998

Infect Immun

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Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates the production of splenic CD8+ effector cells which downregulate delayed hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction and/or elicitation of downregulation was studied by (i) examining murine splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, and gamma interferon (IFN-γ), (ii) quantitating splenocyte mRNA for IL-12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii) measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked immunosorbent assay, each performed at selected intervals over 96 h after giving MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h period, whereas those for IL-4 and IFN-γ were either weak or undetectable prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the downregulatory effect of MAN only when given at the time of MAN administration. Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at 48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s) for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-γ, interacting with MAN-activated cells in the absence of biologically active IL-12, may induce the production of CD8+ downregulatory effector cells. Partial abrogation of downregulatory activity in animals treated with anti-IL-4 at the time of induction of such activity lends support to this hypothesis.

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Regulation of cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response

Cited by 39 publications

References 25 publications

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

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

Alterations in Frequency of Interleukin-2 (IL-2)-, Gamma Interferon-, or IL-4-Secreting Splenocytes Induced byCandida albicansMannan and/or Monophosphoryl Lipid A

Cytokine Involvement in Immunomodulatory Activity Affected byCandida albicansMannan

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