{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:21:29Z","timestamp":1793146889808,"version":"4.5.0"},"reference-count":96,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19 AI166059,R21 AI149654"],"award-info":[{"award-number":["U19 AI166059,R21 AI149654"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014576","name":"University of California Office of the President","doi-asserted-by":"crossref","award":["VFR-19-633386"],"award-info":[{"award-number":["VFR-19-633386"]}],"id":[{"id":"10.13039\/100014576","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Coccidioidomycosis ranges from self-limiting uncomplicated Valley fever (UVF) in most cases to life-threatening disseminated coccidioidomycosis (DCM) in rare individuals. A few patterns of immunologic deficits allowing for dissemination have been identified, although the specific defects in most individuals with DCM remain undefined. We hypothesized that chronic antigen exposure in DCM engenders a state of T cell exhaustion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      From a cohort of over 300 individuals with confirmed diagnoses of coccidioidomycosis, circulating T cell phenotypes were characterized via flow cytometry and\n                      <jats:italic>Coccidioides<\/jats:italic>\n                      -specific T cell responses were measured by activation-induced marker (AIM) assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Male sex was significantly associated with disseminated disease (OR 2.5, 95% CI 1.5\u20134.0). A majority (52%) of individuals showed\n                      <jats:italic>Coccidioides<\/jats:italic>\n                      -specific T cell responses in our AIM assay. We noted a significant difference in patients sampled in the first year of diagnosis, where only 8% of patients with DCM had T cell responses during this time, as compared with 44% of individuals with UVF (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04). Among DCM patients with detectable AIM responses, CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells demonstrated an exhausted phenotype with elevated PD-1 expression compared with UVF individuals. In vitro PD-1 blockade augmented IFN-\u03b3 production in most tested individuals with DCM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These findings suggest that dissemination may occur in some individuals during a period of impaired antigen-specific T cell activity. Importantly, these responses can be augmented in vitro by PD-1\u2013blocking antibodies, supporting further study of immune checkpoint therapy as an adjunct to antifungal treatment in disseminated coccidioidomycosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>National Institute of Allergy and Infectious Diseases grants U19 AI166059 and R21 AI149654 and University of California Office of the President grant VFR-19-633386.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.203270","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:21:49Z","timestamp":1776705709000},"source":"Crossref","is-referenced-by-count":1,"title":["Exhausted T cell phenotypes in disseminated coccidioidomycosis"],"prefix":"10.1172","volume":"11","author":[{"given":"Gregory 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