CD8 TCR ß chain repertoire expansions and deletions are related with immunologic markers in HIV-1-infected patients during treatment interruption.

ABSTRACT

BACKGROUND: HIV-1-infected individuals progressively loss CD4(+) T cells leading to immunosuppression and raising the risk of opportunistic infections. CD8(+) T-cells play an important role in the immune response against virus infections through their TCR. OBJECTIVE: To evaluate the CD8-TCR repertoire and immunologic markers in HIV-1-infected patients. STUDY DESIGN: Ten chronic HIV-1-infected individuals on prolonged effective antiretroviral treatment (ART) were analyzed at baseline (before treatment interruption), after at least one year of treatment interruption (TI) and after at least one year from ART resume (TR). Twenty-four TCR-Vß gene families were analyzed by a modified CDR3 spectratyping method in isolated CD8(+) T-cells. Immune activation, exhaustion and subpopulation markers were analyzed by flow cytometry. RESULTS: Expansion of Vß10, Vß14 and Vß15 families, associated with low cell activation and stable exhaustion markers, were found at TI. Moreover, an increment of effector memory cells was found. Besides, depletion of Vß20, Vß28, and Vß29 families, associated with an increase in cell activation and exhaustion markers, at TI were also found. These alterations seemed to be more pronounced in patients who had longer time from diagnosis. ART seemed to restore altered CD8(+) T-cell repertoire and most of the immunologic markers. CONCLUSIONS: During TI (that was more pronounced in patients with longer HIV-1 infection) it was observed the expansion of Vß families correlated with decreased cell activation, while Vß families correlated with cell activation and exhaustion were depleted. These specific repertoire alterations reverted after ART resume.