IAI Accepts, published online ahead of print on 9 November 2009

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Infect. Immun. doi:10.1128/IAI.00953-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Polyfunctional T lymphocytes are in the peripheral blood of donors naturally immune to coccidioidomycosis and are not induced by dendritic cells.

Lance Nesbit, Suzanne M. Johnson, Demosthenes Pappagianis, and Neil M. Ampel^*

From the Department of Immunobiology, the Department of Medicine, and the Valley Fever Center for Excellence of the University of Arizona; the Department of Microbiology and Immunology of the University of California at Davis, Davis, CA; and the Southern Arizona Veterans Affairs Health Care System (SAVAHCS), Tucson, AZ

^* To whom correspondence should be addressed. Email: nampel{at}email.arizona.edu.

Coccidioidomycosis is an endemic fungal infection of 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 non-immune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular IL-2, IFN- and TNF- 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 non-immune donors (P = 0.03). When monocyte-derived 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 non-immune 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-expressing CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 when PBMC were incubated with the mitogen PHA (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.