T-Cell Subsets (T_CM, T_EM, T_EMRA) and Poly-Functional Immune Response in Patients with Human Immunodeficiency Virus...

Dynamic changes of cytotoxic T cell responses against Human Immunodeficiency Virus 1 (HIV-1) infection have been the subject of an innovative investigation using antiretroviral therapy (ART). Currently, human CD8 naïve central memory (T_CM), effector memory (T_EM), and effector memory cells re-expressing CD45RA (T_EMRA) T-cells have been thoroughly studied with ART. CD45RA is a marker usually found on naïve T-cells.

We performed a longitudinal study of mono-/polyfunctional T-cells in the peripheral blood while targeting three functionally distinct cell populations of CD4⁺ and CD8⁺ T-cells (single IL2 and IFN-γ, dual IL2/IFN-γ) in 50 HIV-1 patients. These patients consisted of 5 controllers, 15 non-controllers, 20 ART responders, and 10 highly active antiretroviral therapy (HAART) non-responders.

We found that (1) non-controllers had the highest rate of IFN-γ-expressing CD4 or CD8, but the lowest rate of IL2-producing CD4 or CD8. (2) The control of HIV-1 infection was associated with polyfunctional Gag-specific T cell responses in controllers and responders. (3) Non-responders had high serum levels of IL2 and IFN-γ. There was a high percentage of CD4⁺ T cell response cells within the less differentiated phenotype in controllers. CD8⁺ T cell showed a high rate of T_EM and T_EMRA in responders.

High levels of pro-inflammatory cytokines are typical in non-responders, exhausted T-cells may be associated with HIV-1 progression.