A shift towards Th2 and changes in the distribution into Tnaϊve, TCM, TEM, and TEMRA subsets in HIV-infected non-responders.

Abstract

The decrease in CD4⁺ T-cell count, as well as a shift of Th1/Th2 towards Th2, are typical for HIV-infected people before treatment and associated with increased mortality risks. Studies of Th2 frequencies in HIV-infected patients receiving highly-active antiretroviral therapy (ART) have shown conflicting results and did not take into account CD4⁺ T-cell counts. We qualified the frequencies of Th1 (CD4⁺T-bet⁺IFNγ⁺) and Th2 (CD4⁺GATA-3⁺IL-4⁺) in HIV-infected individuals on ART using flow cytometry, considering the efficiency of CD4⁺ T-cell recovery. Additionally, we assessed the expression of CCR7 and CD45RO to determine the effector potential of the studied cells. We found that immunological non-responders (INRs), with CD4⁺ T-cell count <350 cells/μL, have increased frequencies of Th2 (Median (Me) = 3.35 %) compared to complete responders (CRs), with CD4⁺ T-cell count >500 cells/μL (Me = 2.52 %, p = 0.035) and HIV-negative individuals (Me = 2.19 %, p = 0.007). This, along with a decrease in the number of Th2 in INRs (Me = 6.9 cells/μL), compared to CRs (Me = 14.0 cells/μL, p = 0.027) and HIV-negative individuals (Me = 15.8 cells/μL, p = 0.009), indicates differential regulatory processes that ensure the Th2 survival not only in the early stages of HIV infection, but also during long-term ART. Furthermore, the distribution of peripheral blood CD4⁺, Th1 and Th2 cells into T_naϊve/T_CM/T_EM/T_EMRA subsets varied significantly: approximately half of CD4⁺ T-cell are naive, the majority of Th1 are T_EM and the most numerous population of Th2 is T_CM. INRs demonstrated a decrease in naive CD4⁺ T-cells (Me = 38.9 %, p = 0.041), compared to CRs Me = 57.7 %) and reduction of naive Th2 cells (Me = 11.4 %, p = 0.049), compared to CRs Me = 16.9 %). In addition, we note some minor expansion of T_EM cells among Th1 and Th2 in INRs. Correlation analysis demonstrated a positive relationship between Th1 and Th1 T_EM (r = 0.85, p = 0.003) frequencies, as well as negative correlations between Th2 and Th2 T_CM (r = -0.71, p = 0.027), Th1 and Th1 naive (r = -0.92, p = 0.0004) and CD4⁺ and CD4⁺T_EM (r = -0.66, p = 0.044) frequencies in INRs. Evidently, the CD4⁺ T-cell deficiency in INRs is associated with subset-specific alterations, which may include shifts in the cell frequencies and effector potential.