Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

Abstract

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4 + T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH.We characterized the TCR V-J pairing profile of naïve and memory CD4 + T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection. acquired immune deficiency syndrome, human immunodeficiency virus, antiretroviral therapy, T cell receptor, V-J pairing

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir

“…PLWH have decreased CD4 + T cell populations, and studies have shown that those on short-term ART regimens (3 months) were unable to restore TCR diversity, compared with healthy individuals ( 27 , 28 ). When evaluating TCR diversity, lymphocyte-depleting therapy correlates with early repertoire turnover, almost certainly due to the massive decrease in overall T cell populations initially, followed by clonal expansion of often newly detected TCR rearrangements to compensate for loss of T cells.…”