Severe immune dysregulation affects CD4 +CD25 hiFoxP3 + regulatory T cells in HIV-infected patients with low-level CD4 T-Cell repopulation despite suppressive highly active antiretroviral therapy

摘要

We hypothesized that CD4 +CD25 hiFoxP3 + regulatory T cells (Tregs) could be involved in the high immune activation existing in patients with low-level CD4 T-cell repopulation under suppressive high active antiretroviral therapy (hereafter, "LLR patients"). Sixteen LLR patients, 18 human immunodeficiency virus (HIV)-infected controls (hereafter, "HIV controls"), and 16 healthy subjects were included. The frequency of CD4 +CD25 hiFoxP3 + and HIV-specific Treg suppressive function were assessed. Relationships between Treg and CD4/CD8 activation (HLA-DR/CD38) and the frequency of naive CD4 T-cells were assessed. Low-level patients showed a higher Treg frequency but reduced HIV-specific immunosuppressive functions than HIV controls. Whereas in healthy subjects a strong negative correlation between Tregs and activated CD8 T cells emerged (r =-0.75, P . 001), it appeared disrupted in both HIV-infected groups (r =-0.06 and P =. 83 for LLR patients; r =-0.11 and P =. 68 for and HIV controls). Nevertheless, in LLR patients, Tregs negatively correlated with naive CD4 T cells (r =-0.60, P =. 01), whereas there was no such correlation in HIV controls (r =-0.19, P =. 46) or healthy subjects (r =-0.10, P =. 73). Remarkably, a higher ratio of Tregs to naive CD4 T cells was observed in LLR patients than in HIV controls (P =. 001) and healthy subjects (P . 001). We conclude that LLR patients have important alterations in immunoregulation involving CD4 +CD25 hiFoxP3 + Tregs. In this scenario, the role of Tregs seems to be more related to the control of the naive CD4 T-cell homeostatic proliferation, rather than to the immune activation.