{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T23:58:28Z","timestamp":1775519908632,"version":"3.50.1"},"reference-count":103,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"crossref","award":["BT\/PR28416\/MED\/29\/1310\/2018"],"award-info":[{"award-number":["BT\/PR28416\/MED\/29\/1310\/2018"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | National Institutes of Health","award":["ICIDR 1UO1A\/115654"],"award-info":[{"award-number":["ICIDR 1UO1A\/115654"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2023,11,30]]},"abstract":"ABSTRACT<\/jats:title>\n \n CD8 T cells are important tools for protection against intracellularly replicating pathogens such as viruses. Previous studies showed that a discrete population of HLADR and CD38-expressing CD8 T cells expands massively during the acute febrile phase of human dengue virus infection\u2014but very few of these cells secrete IFN\u03b3 upon\n in vitro<\/jats:italic>\n stimulation with dengue peptides. To gain a better understanding of what other cytokines\/chemokines do these massively expanding HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n CD8 T cells express, we performed RNA seq of sorted HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n CD8 T cell subsets after peptide stimulation. A majority of these peptide-stimulated HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n CD8 T cells were CD69\n -<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n , nearly a third were CD69\n +<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n , whereas very few (<10%) were CD69\n +<\/jats:sup>\n IFN\u03b3\n +<\/jats:sup>\n . The CD69\n -<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n subset was enriched for the expression of key genes implicated in the negative regulation of T cell receptor (TCR) signaling and T-cell exhaustion, attraction of B cells and other lymphocytes, and cytokines related to Tc17\/T-reg lineages or those that are implicated in immunosuppression\/immunomodulatory and anti-inflammatory activities and angiogenesis. The CD69\n +<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n subset showed enriched transcription of key genes implicated in cytotoxic effector functions as well as costimulatory and signaling adaptors implicated in fine balancing of T cell receptor signaling. The CD69\n +<\/jats:sup>\n IFN\u03b3\n +<\/jats:sup>\n subset largely shared the transcriptional profile with the CD69\n +<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n subset\u2014but with relatively more pronounced expression along with additional genes such as chemokines XCL1\/XCL2. Our findings showing distinct functional subsets among these massively expanding CD8 T cells in dengue CD8 T cells warrant further studies to carefully examine the precise role of these T cell subsets in protection against dengue.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFN\u03b3). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection. Although about a third of these massively expanding HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n CD8 T cells were also CD69\n high<\/jats:sup>\n when examined\n ex vivo<\/jats:italic>\n , only a small fraction of them produced IFN\u03b3 upon\n in vitro<\/jats:italic>\n peptide stimulation. Therefore, to better understand such functional diversity of CD8 T cells responding to dengue virus infection, it is important to know the cytokines\/chemokines expressed by these peptide-stimulated HLADR\n +<\/jats:sup>\n CD38\n +<\/jats:sup>\n CD8 T cells and the transcriptional profiles that distinguish the CD69\n +<\/jats:sup>\n IFN\u03b3\n +<\/jats:sup>\n , CD69\n +<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n , and CD69\n -<\/jats:sup>\n IFN\u03b3\n -<\/jats:sup>\n subsets.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/jvi.00746-23","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T12:58:58Z","timestamp":1697720338000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Functional and transcriptional heterogeneity within the massively expanding HLADR\n +<\/sup>\n CD38\n +<\/sup>\n CD8 T cell population in acute febrile dengue 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