Griffith Gina L, Machmach Kawthar, Jian Ningbo, Kim Dohoon, Costanzo Margaret C, Creegan Matthew, Swafford Isabella, Kundu Gautam, Yum Lauren, Bolton Jessica S, Smith Lauren, Slike Bonnie M, Bergmann-Leitner Elke S, Thomas Rasmi, Michael Nelson L, Ake Julie A, Eller Leigh Anne, Robb Merlin L, Townsley Samantha M, Krebs Shelly J, Paquin-Proulx Dominic
US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
PLoS Pathog. 2025 Jan 31;21(1):e1012916. doi: 10.1371/journal.ppat.1012916. eCollection 2025 Jan.
New HIV vaccine approaches are focused on eliciting broadly neutralizing antibodies. We characterized early gamma-delta (γδ) T cell responses starting from pre-acquisition and during acute HIV infection (AHI) in participants previously characterized for neutralization breadth development. We found significant differences in γδ T cell surface marker expression in participants that developed neutralization breadth compared to those that did not. Activation of γδ T cells occurred within the first weeks of HIV acquisition and associated with viral load. Expression of CD16 on Vδ1 T cells and CD57 on Vδ2 T cells were found to be significantly higher in broad neutralizers during AHI, and associated with the development of neutralization breadth years later. In addition, the levels of CD16 on Vδ1 T cells was associated with early production of founder virus Env-specific IgM. Thus, γδ T cells may promote development of neutralization breadth, which has implications for HIV vaccine strategies.
新型HIV疫苗的研发方向聚焦于诱导产生广泛中和抗体。我们对先前已根据中和广度发展情况进行特征描述的参与者，从感染前到急性HIV感染（AHI）期间的早期γδ T细胞反应进行了表征。我们发现，与未产生中和广度的参与者相比，产生中和广度的参与者在γδ T细胞表面标志物表达上存在显著差异。γδ T细胞的激活发生在HIV感染后的头几周内，且与病毒载量相关。发现在AHI期间，广泛中和者的Vδ1 T细胞上CD16的表达以及Vδ2 T细胞上CD57的表达显著更高，并且与数年后中和广度的发展相关。此外，Vδ1 T细胞上CD16的水平与创始病毒Env特异性IgM的早期产生有关。因此，γδ T细胞可能促进中和广度的发展，这对HIV疫苗策略具有重要意义。
