HIV-1–specific CD8⁺ T-cell responses are impaired in cytokine production in the presence of sE-cadherin. Intracellular cytokine staining was used to determine whether the presence of sE-cadherin inhibits the function of Gag-specific CD8⁺ T cells. (A) Example of a Gag-specific CD8⁺ T-cell response in the presence or absence of sE-cadherin as well as the cumulative differences of all studied subjects with chronic HIV-1 infection (n = 13). In the presence of sE-cadherin, Gag-specific IFN-γ responses were significantly impaired (P = .002 paired t test). The numbers in each quadrant represent the % frequency of the parent. Similar results were obtained when assessing IFN-γ responses by Luminex (P = .004; B). Reduction in IFNγ secretion on E-cadherin ligation was most pronounced on KLRG1⁺ CD8⁺ T cells and also induced a KLRG1 down-regulation. The numbers in each quadrant represent the % frequency of the parent (C). However, no differences were observed for the TNF-α responses in the presence or absence of sE-cadherin (P = ns; D).