Modulation of TIM-3 expression on NK and T cell subsets in HIV immunological non-responders

•HIV IRs and INRs show increased galectin-9 expression on NK and CD4+ T cells.•INRs have less CD16+CD56+ and CD16+CD56− NK cells that express TIM-3 than HIV IRs.•The frequency of TIM-3+CD4+ cells in PBMC is reduced in INRs compared to HIV IRs.•TIM-3 expression on NK and T cells correlates with peripheral CD4 count.

Highly active antiretroviral therapy (HAART) for the treatment of HIV infection sustains viral suppression and increases CD4+ T cells in HIV patients. However, in 10-25% of subjects, known as immunological non-responders (INRs), HAART does not increase CD4 count. We investigated a potential role for galectin-9 and TIM-3 in INRs as galectin-9 and TIM-3 have been described to modulate NK and T cell function. PBMCs were isolated from healthy controls, HIV immunological responders (IRs, > 350 CD4+ cells/mm3) and HIV INRs (< 350 CD4+ cells/mm3) and TIM-3 and galectin-9 expressions on NK cell subsets and CD4+ T cells were assessed. HIV INRs and HIV IRs showed increased galectin-9 expression on CD16−CD56bright and CD16+CD56+ NK cells and CD4+ T cells. Only HIV INRs showed a reduced frequency of TIM-3-expressing CD16+CD56+, CD16+CD56− and CD4+ cells, which correlated with low peripheral CD4 counts. These data suggest that TIM-3 expression may be characteristic for HIV INRs.