γδ T cells mediate robust anti-HIV functions during antiretroviral therapy regardless of immune checkpoint expression.

Objectives: Although antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.

Methods: Utilising a cohort of ART-treated PLWH, we assessed the frequency and phenotype, characterised functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells.

Cytokines enhance human Vγ9Vδ2 T-cell TCR-dependent and TCR-independent effector functions.

Vγ9Vδ2 T cells can recognize various molecules associated with cellular stress or transformation, providing a unique avenue for the treatment of cancers or infectious diseases. Nonetheless, Vγ9Vδ2 T-cell-based immunotherapies frequently achieve suboptimal efficacies in vivo. Enhancing the cytotoxic effector function of Vγ9Vδ2 T cells is one potential avenue through which the immunotherapeutic potential of this subset may be improved.

Establishment and recall of SARS-CoV-2 spike epitope-specific CD4 T cell memory.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4 T cell responses to the spike protein, including circulating follicular helper T (cT) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S tetramer to track spike-specific CD4 T cells, we show that primary infection or vaccination induces robust S-specific CXCR5 and cT cell memory responses. Secondary exposure induced recall of CD4 T cells with a transitory CXCR3 phenotype, and drove expansion of cT cells transiently expressing ICOS, CD38 and PD-1.