美国国立卫生研究院
研究人员详细揭示了疫苗诱导的HIV特异性CD8+ T细胞的功能。细胞毒性能力明显低于HIV控制者，这并不是频率低或功能性细胞毒性蛋白未积累的结果。细胞毒性能力低的原因是，HIV感染目标上的抗原水平低，导致脱颗粒功能受损。疫苗诱导的T细胞受体（TCR）是多克隆的，转导这些TCR也会导致功能降低。
这些结果确定了这些疫苗诱导的抗病毒活性低下的机制，并表明有效的CD8+ T细胞应答可能需要一种能进一步推动TCR克隆选择的疫苗接种策略。
据了解，目前旨在刺激CD8+ T细胞的HIV疫苗未能在感染后诱导免疫控制。
附：英文原文
Title: HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity
Author: Stephen A. Migueles, Danielle M. Nettere, Noah V. Gavil, Lawrence T. Wang, Sushila A. Toulmin, Elizabeth P. Kelly, Addison J. Ward, Siying Lin, Sarah A. Thompson, Bennett A. Peterson, Cassidy S. Abdeen, Carina R. Sclafani, Patrick F. Pryal, Benjamin G. Leach, Amanda K. Ludwig, Daniel C. Rogan, Paulina A. Przygonska, Angela Cattani, Hiromi Imamichi, Abraham Sachs, Gal Cafri, Ning-Na Huang, Andy Patamawenu, C. Jason Liang, Claire W. Hallahan, Diane M. Kambach, Edward X. Han, Tiffany Coupet, Jonathan Chen, Susan L. Moir, Tae-Wook Chun, Emily E. Coates, Julie Ledgerwood, Julien Schmidt, Marie Taillandier-Coindard, Justine Michaux, HuiSong Pak, Michal Bassani-Sternberg, Nicole Frahm, M. Juliana McElrath, Mark Connors
Issue&Volume: 2023-12-15
Abstract: Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection.
DOI: adg0514
Source: https://www.science.org/doi/10.1126/science.adg0514