CD4+CD38+ central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART

Abstract

Abstract Background Despite the effective antiretroviral treatment (ART) of HIV-infected individuals, HIV persists in a small pool. Central memory CD4 + T cells (Tcm) make a major contribution to HIV persistence. We found that unlike HLA-DR, CD38 is highly expressed on the Tcm of HIV-infected subjects receiving ART for > 5 years. It has been reported that the half-life of total and episomal HIV DNA in the CD4 + CD38 + T cell subset, exhibits lower decay rates at 12 weeks of ART. Whether CD38 contributes to HIV latency in HIV-infected individuals receiving long-term ART is yet to be addressed. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of HIV-infected subjects receiving suppressive ART. The immunophenotyping, proliferation and apoptosis of CD4 + T cell subpopulations were detected by flow cytometry, and the level of CD38 mRNA and total HIV DNA were measured using real-time PCR and digital droplet PCR, respectively. A negative binomial regression model was used to determine the correlation between CD4 + CD38 + Tcm and total HIV DNA in CD4 + T cells. Results CD38 was highly expressed on CD4 + Tcm cells from HIV infected individuals on long-term ART. Comparing with HLA-DR − Tcm and CD4 + HLA-DR + T cells, CD4 + CD38 + Tcm cells displayed lower levels of activation (CD25 and CD69) and higher levels of CD127 expression. The proportion of CD38 + Tcm, but not CD38 − Tcm cells can predict the total HIV DNA in the CD4 + T cells and the CD38 + Tcm subset harbored higher total HIV DNA copy numbers than the CD38 − Tcm subset. After transfected with CD38 si-RNA in CD4 + T cells, the proliferation of CD4 + T cells was inhibited. Conclusion The current date indicates that CD4 + CD38 + Tcm cells contribute to HIV persistence in HIV-infected individuals on long-term ART. Our study provides a potential target to resolve HIV persistence.

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