Longitudinal changes of peripheral blood DC subsets and regulatory T cells in Chinese chronic HIV-1-infected patients during antiretroviral therapy

Abstract

It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs) and regulatory T cells (Tregs) should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART), and compared with those in healthy controls and long term non-progressors (LTNPs). Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs) increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs) remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.

Figure 1. Longitudinal changes in DC subsets and IFN-a plasma levels during ART (weeks).

(A–C) Longitudinal changes in counts of mDCs, pDCs and IFN-a plasma levels in HIV-1-infected patients during ART. (D–F) Comparisons of mDCs, pDCs and IFN-a plasma levels among HIV-1-infected patients at week 0, week 60, healthy controls and LTNPs. **p<0.01, *p<0.05.

Figure 2. The association of DC subsets with viral loads and CD4+Tcells.

(A–B) Correlation between DC subsets counts and plasma viral loads, CD4+Tcells counts during ART. (C–D) Correlation between change in counts of DC subsets at week 8 and the change in plasma viral loads, CD4+Tcells counts at week 60 post ART.

Figure 3. Longitudinal changes in the percentage and counts of Tregs during ART (weeks).

(A–B) Longitudinal changes in the percentage and counts of Tregs in HIV-1-infected patients during ART. (C–D) Comparisons of the percentage and counts of Tregs among HIV-1-infected patients at week 0, week 60, healthy controls and LTNPs. **p<0.01, *p<0.05.

Figure 4. The association of DC subsets with Tregs percentage.

(A) Correlation between mDCs counts and Tregs percentage during ART. (B) Correlation between pDCs counts and Tregs percentage during ART.

Figure 5. Rare event analysis of DC subsets by flow cytometry: mDCs (R3) and pDCs (R4).

Figure 6. Representative plots of CD4+CD25+FoxP3+Tregs from individual subjects in the HIV-1-infected patients at week 0, week 60, healthy controls and LTNPs.