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

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.

Biologic Agents in Crohn’s Patients Reduce CD4+ T Cells Activation and Are Inversely Related to Treg Cells

“…CD38 is a surface marker most prevalent on cells associated with regulatory activity, such as T regulatory cells and central memory T cells [ 20 ]. We have little information about CD4 + CD38 + cells in IBD, but Song and colleagues [ 21 ] demonstrated an association of such cells with HIV proliferation and persistence in patients receiving antiretroviral therapy. The authors correlate the expression of CD38 on central memory T cells with increased proliferation and survival, thus rendering cells reservoir of HIV.…”

Usefulness of the New Hematological Parameter: Reactive Lymphocytes RE-LYMP with Flow Cytometry Markers of Inflammation in COVID-19

“…It seemed, therefore, that low levels of CD4+ CD38+ cells in COVID-19(+) patients could distinguish these patients from other inflammatory diseases. Song C. B., et al [ 45 ] have shown that CD38 promotes proliferation in the CD4+ T cells of HIV-infected individuals. High levels of human virus-specific CD38+ CD4+ T cells have been reported to be transiently present during acute presentations also of other infections such as: CMV or EBV infections [ 1 , 46 ].…”

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

“…During HIV-1 infection, activated platelets can also form aggregates, conjugates or complexes with CD4 + and CD8 + T cells (56,57), and in particular with memory T cells that are HLA-DR + and CD38 + (17). HLA-DR and CD38 are activation markers on T cells during HIV-1 infection (58). Platelets with engulfed virus particles may also form aggregates with CD16 + inflammatory monocytes (17).…”