{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:40:15Z","timestamp":1764996015527},"reference-count":52,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The interplay between dendritic cells (DC) and \u03b3\u03b4 T lymphocytes represents a network of paracrine and cell contact interactions important for an integrated immune response to pathogens. HIV-1 infection dramatically affects the number and functions of both cell populations, and DC\/\u03b3\u03b4 T cell cross talk may represent a target of virus-induced immune escape. We investigated whether HIV-exposed DC could deliver aberrant signals to interacting \u03b3\u03b4 T cells. Here we report that the interaction of human \u03b3\u03b4 T lymphocytes with HIV-1-exposed autologous monocyte-derived DC, but not direct exposure to the virus, impairs lymphocyte expansion and gamma interferon (IFN-\u03b3) production in response to phosphoantigens. This effect is independent of virus strain and occurred in 55% of the donors analyzed. The donor-dependent variation observed relies on the responsiveness of DC to HIV-1 and is strictly related to the capacity of the virus to suppress the maturation-induced expression of interleukin 12 (IL-12). In fact, \u03b3\u03b4 T cell response to phosphoantigens is almost completely recovered when this cytokine is exogenously added to the DC\/lymphocyte cocultures. Interestingly, we show that \u03b3\u03b4 T lymphocytes are recruited by HIV-1-exposed DC through a CCR5-mediated mechanism and exert a CCL4-mediated control on virus dissemination within DC and susceptible CD4<jats:sup>+<\/jats:sup>T lymphocytes. These results demonstrate an association between HIV-induced DC dysfunction and alterations of \u03b3\u03b4 T cell responses. The aberrant cross talk between these two cell populations may contribute to the pathogenesis of HIV infection by further reducing the strength of antiviral immune response.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>This study provides new evidence on the mechanisms exploited by HIV-1 to evade the host immune response. We report that HIV-1 impairs the cross talk between DC and \u03b3\u03b4 T lymphocytes, by reducing the capacity of DC to promote functional \u03b3\u03b4 T cell activation. Interestingly, the virus does not<jats:italic>per se<\/jats:italic>interfere with \u03b3\u03b4 T cell activation, thus highlighting the key role of early DC\u2013HIV-1 interaction in this phenomenon. Furthermore, the results obtained unravel the novel role of \u03b3\u03b4 T cells in controlling HIV-1 dissemination within the DC population as well as virus transfer to susceptible CD4<jats:sup>+<\/jats:sup>T lymphocytes. The interactions of DC with innate lymphocytes represent a major control mechanism for an integrated immune response to infection. Understanding how HIV-1 harnesses these pathways may provide important insights on the pathogenesis of disease and offer new opportunities for therapeutic interventions.<\/jats:p>","DOI":"10.1128\/jvi.03681-14","type":"journal-article","created":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T06:52:40Z","timestamp":1423723960000},"page":"4798-4808","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["HIV-1-Induced Impairment of Dendritic Cell Cross Talk with \u03b3\u03b4 T Lymphocytes"],"prefix":"10.1128","volume":"89","author":[{"given":"Marco","family":"Cardone","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyojiro N.","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Varano","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Gessani","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2012.02727.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2012.43"},{"key":"e_1_3_2_4_2","first-page":"206","article-title":"T cell receptor gamma\/delta+ lymphocyte subsets during HIV infection","volume":"75","author":"Autran B","year":"1989","unstructured":"Autran B, Triebel F, Katlama C, Rozenbaum W, Hercend T, Debre P. 1989. 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