Impact of ART on CD4⁺/CD8⁺ T-cell-specific response to copathogens in HIV-TB patients

Abstract

Background: HIV is a risk factor for tuberculosis (TB) disease. Antiretroviral therapy (ART) induces rapid suppression of HIV replication but it is still unclear the extent to which pre-existing copathogen specific T-cells are restored.

Aim: To evaluate the impact of ART in HIV-infected patients with or without active TB or latent TB infection (LTBI) on the function and phenotypic profile of M. tuberculosis (Mtb)-specific antigen-response of CD4⁺ and CD8⁺ T-cells in comparison with other recall antigen responses. The analysis was performed before and 1 year after ART initiation.

Methods: PBMCs were stimulated overnight with Mtb antigens (RD1), HIV antigens (GAG), cytomegalovirus (CMV), and staphylococcal enterotoxin B (SEB) to perform FACS analysis evaluating the cytokine expression (IFN-γ, TNF-α and IL-2) and the phenotypic profile.

Results: In the HIV-LTBI and HIV-TB, ART increased the number of responders to Mtb, HIV-GAG and CMV within both the CD4⁺ and CD8⁺ T-cell compartment. Moreover, ART significantly increased the frequency of Mtb-specific CD4⁺ T-cells response in the HIV-LTBI (p=0.015) with an increase of the central memory (CM) compartment. The magnitude of the CD4⁺ T-cells response to HIV-GAG significantly increased in the active TB (p=0.03) patients.

Conclusion: ART increases the response to all recall antigens in HIV-LTBI and HIV-TB patients in both CD4⁺ and CD8⁺ T-cells. Interestingly ART increases also the magnitude of Mtb-specific response in HIV-LTBI within the CD4 T-cell and this correlated with an increase in the (CM) compartment. These results improve our understanding on TB pathogenesis and impact of ART with new potentials for clinical management of co-infections.