Severe Immune Dysregulation Affects CD4 super(+)CD25 super(hi)Fox P3 super(+) Regulatory T Cells in HIV-Infected Patients With Low-level CD4 T-Cell Repopulation Despite Suppressive Highly Active Antiretroviral Therapy

• Published in: The Journal of infectious diseases 2012-05, Vol.205 (10), p.1501-1509
• Main Authors: Mendez-Lagares, Gema, Balado, Maria del Mar del Pozo, Gonzalez, Miguel Genebat, Sanchez, Antonio Garcia Perganeda, Noval, Manuel Leal, Lopez, Yolanda Maria Pacheco
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis230

We hypothesized that CD4 super(+)CD25 super(hi)Fox P3 super(+) 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 super(+)CD25 super(hi)Fox P3 super(+) 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 super(+)CD25 super(hi)Fox P3 super(+) 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.