In vitro modulation of cytokine production by lymphocytes in human coccidioidomycosis

Ampel, Neil M.; Kramer, Larissa A

doi:10.1016/s0008-8749(03)00067-4

Cited by 17 publications

(10 citation statements)

References 16 publications

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“…We cannot say for certain how our findings in mice relate to the human response to this fungus, but there are some parallels between human and mouse responses to the fungus. Ampel and Kramer analyzed the responses of peripheral blood mononuclear cells to T27K, a soluble antigen from spherules 16 . They found that healthy immune donors respond by making IFNγ, and that exogenous IL‐10 inhibits that response, which is what we found in the IL‐10 transgenic mice.…”

Section: Immune Responses Of Inbred Mice To C Immitis Infectionsupporting

confidence: 68%

The Role of IL‐10 in Genetic Susceptibility to Coccidioidomycosis on Mice

Fierer

2007

Annals of the New York Academy of Sciences

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Epidemiological and clinical studies have confirmed that coccidioidomycosis is more severe in African American and Filipino patients than in Caucasians, suggesting a genetic basis for susceptibility in humans. We discovered that inbred strains of mice also vary greatly in their susceptibility to Coccidioides immitis infections, and although resistance is the dominant phenotype, it is a multigenic trait in mice. We found a strong direct correlation between susceptibility in mice and the amount of IL-10 made in response to infection. We then showed that IL-10-deficient mice are much more resistant to infection than the parent C57BL/6 strain. Finally, we showed that genetically resistant mice that are transgenic for IL-10 and so overproduce that cytokine are more susceptible to C. immitis. This is in part due to suppression of NOS2 expression by IL-10.

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Section: Immune Responses Of Inbred Mice To C Immitis Infectionsupporting

confidence: 68%

The Role of IL‐10 in Genetic Susceptibility to Coccidioidomycosis on Mice

Fierer

2007

Annals of the New York Academy of Sciences

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“…[34][35][36][37] The clinical course may be greatly influenced by whether the immune response is directed predominantly towards a T H 1 pattern or towards a T H 2 pattern. 37 Interferon-gamma, a T H 1-associated cytokine, activates macrophages, which are subsequently able to inhibit or kill the organisms.…”

Section: Immune Responsementioning

confidence: 99%

Coccidioidomycosis: A review and update

DiCaudo

2006

Journal of the American Academy of Dermatology

112

104

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“…Moreover, this cellular immune response appears to be long-lived and protective (15). In vitro studies have suggested that control of infection is associated with the release of T-helper type 1 (Th1) cytokines, such as interleukin-2 (IL-2) and gamma interferon (IFN-␥), from peripheral blood mononuclear cells (PBMC) (1)(2)(3)(4)(5)13).…”

mentioning

confidence: 99%

“…In that study, the mature dendritic cells (mDC) generated were functionally and phenotypically normal. Stimulation in this model was accomplished using T27K, an antigen preparation derived from Coccidioides posadasii that specifically induces the release of Th1 cytokines from PBMC from healthy immune donors (3)(4)(5) and correlates with DTH responses (6).…”

mentioning

confidence: 99%

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Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

et al. 2010

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Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-␥), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P ‫؍‬ 0.03). When monocytederived mature dendritic cells pulsed with T27K (mDC T27K ) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDC T27K did significantly increase the concentrations of IL-2 and IFN-␥ released by PBMC from nonimmune donors (P ‫؍‬ 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low-and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P ‫؍‬ 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.

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In vitro modulation of cytokine production by lymphocytes in human coccidioidomycosis

Cited by 17 publications

References 16 publications

The Role of IL‐10 in Genetic Susceptibility to Coccidioidomycosis on Mice

The Role of IL‐10 in Genetic Susceptibility to Coccidioidomycosis on Mice

Coccidioidomycosis: A review and update

Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

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