{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:04:31Z","timestamp":1784898271767,"version":"3.55.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["HL152576"],"award-info":[{"award-number":["HL152576"]}]},{"name":"National Institute of Health","award":["AI015614"],"award-info":[{"award-number":["AI015614"]}]},{"name":"School of Medicine, University of Colorado Denver","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Ann Theodore Foundation Breakthrough  Sarcoidosis Initiative","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"NIH","award":["HL152576"],"award-info":[{"award-number":["HL152576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:p>\n                    In chronic beryllium disease (CBD), elevated levels of the inflammatory chemokines CCL3 and CCL4 in the lungs coincide with expanded populations of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells specific to beryllium-modified (Be-modified) peptides derived from these chemokines. Here, we generated HLA-DP2 transgenic (Tg) CCL3-deficient mice (CCL3\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) that also lack CCL4 to investigate their role in disease development. Be-exposed CCL3\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice maintained normal numbers of lung macrophages and dendritic cells (DCs) but exhibited significantly reduced total and HLA-DP2\u2013CCL\/Be tetramer-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, IFN-\u03b3\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and peribronchovascular aggregates, consistent with attenuated inflammation. CCL3 was predominantly expressed in macrophages and DCs, and bone marrow chimera studies confirm that hematopoietic-derived DCs are the key regulators of CCL\/Be-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses. RNA-seq of lung-resident CCL4\/Be tetramer\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells revealed a transcriptional profile enriched for inflammatory and cholesterol-metabolism pathways, with elevated expression of\n                    <jats:italic>Ifng<\/jats:italic>\n                    ,\n                    <jats:italic>Tnf<\/jats:italic>\n                    , and\n                    <jats:italic>Il17a<\/jats:italic>\n                    . Moreover, Be-exposed HLA-DP2 Tg mice lacking TNF-\u03b1 or treated with peptide-MHCII CAR-T cells targeting CCL4\/Be-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells showed reduced T cell responses and cellular aggregates. These findings demonstrate that CCL3 and CCL4 promote CCL\/Be-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses and highlight peptide-MHCII CAR-T cells as a potentially novel strategy for depleting self-peptide\/Be-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in CBD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195868","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:13:22Z","timestamp":1781018002000},"source":"Crossref","is-referenced-by-count":0,"title":["Reduced CCL\/Be-specific CD4+ T cells in CCL3-deficient or peptide-MHCII CAR-T cell\u2013treated mice"],"prefix":"10.1172","volume":"11","author":[{"given":"Michael T.","family":"Falta","sequence":"first","affiliation":[{"name":"Department of Medicine 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