Preliminary Evaluation of Whole-Blood Gamma Interferon Release for Clinical Assessment of Cellular Immunity in Patients with Active Coccidioidomycosis

Abstract

Assessment of the cellular immune response in coccidioidomycosis has epidemiologic and prognostic importance. Measurement of delayed-type hypersensitivity to skin testing has been used in the past to determine cellular immunity in coccidioidomycosis. However, no skin tests are currently available in the United States. Assay of gamma interferon (IFN-␥) release in whole blood in response to incubation with antigen has been used to assess cellular immunity in tuberculosis. We used a similar assay using the coccidioidal antigen preparation T27K to measure the in vitro cellular immune responses among a cohort of 69 subjects with active coccidioidomycosis. IFN-␥ release was bimodal, with concentrations above and below 5 IU/ml. Using multivariate logistic regression, underlying disease and disseminated or chronic pulmonary coccidioidomycosis was significantly associated with the release of IFN-␥ at a concentration of <5 IU/ml (P ‫؍‬ 0.02 or 0.05, respectively). In addition, the release IFN-␥ concentration was <5 IU/ml in all subjects with a clinical severity score of >6 (P ‫؍‬ 0.02). The release IFN-␥ concentration correlated with expression of CD69 on T lymphocytes in an in vitro assay using T27K as the antigen (Spearman's rho ‫؍‬ 0.59; P < 0.01). These results suggest that the IFN-␥ release assay with T27K as the antigen may be a useful clinical test for assessing cellular immunity in patients with active coccidioidomycosis.

Host–Pathogen Interactions in Coccidioidomycosis: Prognostic Clues and Opportunities for Novel Therapies

“…Peripheral blood cells from patients with DCM produce less IFN-g in response to Coccidioides antigen than cells from those with milder disease. 58,59 Treatment of mice with IFN-g was able to protect mice from systemic infection. 60 A few human patients with extrapulmonary disease have been treated successfully with IFN-g as well (as discussed later), supporting the importance of this cytokine in fighting CM.…”

Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis

“…Based on previous observations (12,13), it was surprising that Th1 cytokines in subjects with nonmeningeal disseminated coccidioidomycosis were similar to those in subjects with pulmonary disease and healthy immune donors. To explore this further, we examined cytokine concentrations based on the time from diagnosis to the time of assay.…”

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

“…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).…”

“…Finally, we attempted to ascertain the memory phenotype of antigen-stimulated lymphocytes from naturally immune donors. In all of this work, we used the antigen preparation T27K, since it has consistently been shown to induce specific Th1 responses from coccidioidal antigen immune individuals (3)(4)(5).…”

“…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).…”