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

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, >350CD4⁺ cells/mm³) and HIV INRs (<350CD4⁺ 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^-CD56^bright 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.