THAA0306 | REGULATORY T CELLS IN HIV-1 INFECTION: IMPLICATIONS FOR IMMUNE REGULATION AND THERAPEUTIC POTENTIAL

Georgia Elna Ambada Ndzengue¹, Aubin Nanfack¹, Stephanie Sake², Loveline Ngu³, Abel Lissom⁴, Jules Tchadji¹, Martin Sosso¹, François-Xavier Etoa², Godwin Nchinda¹ | ¹Chantal Biya International Reference Centre (CIRCB) for Research on HIV and AIDS Prevention and Management, Yaounde, Cameroon; ²Department of Microbiology, University of Yaounde I, Yaounde, Cameroon; ³Department of Biochemistry, University of Yaounde I, Yaounde, Cameroon; ⁴Faculty of Science, University of Bamenda, Bamenda, Cameroon

In steady states, regulatory T (Treg) cells are expected to dampen excessive immune activation. However, their total number decreases proportionally with helper CD4⁺ T cells, while their proportions remain elevated in HIV-1-infected individuals. It is unclear whether the discrepancies in Treg cell numbers and frequencies indicate a deficiency in their functionality. To address this issue, Treg cells were assessed for their capacity to regulate the activation of autologous monocytes, as well as their ability to produce pro-inflammatory cytokines when stimulated with poly-ICLC, a TLR3 and MD5 agonist. Treg cells and monocytes were isolated from peripheral blood mononuclear cells collected from 40 ART-naïve HIV-1-infected adults and 20 control subjects and subsequently co-cultured with poly-ICLC. Flow cytometry was used to assess the cytokine profile of Treg cells, the activation status of monocytes, and their cytokine production. The inhibitory function of Treg cells was measured through the suppression index. Statistical analyses were conducted using Graph Pad Prism 6 software. Treg cells exhibit the ability to reduce CD38 expression, IL-6, and TNF-alpha production levels. The suppression index of Treg cells demonstrated a positive correlation with CD4 counts (r = 0.68, p < 0.0001 for CD38; r = 0.6, p= 0.0001 for IL-6; and r = 0.67, p < 0.0001 for TNF-alpha) and a negative correlation with HIV-1 plasma viral loads (r = -0.45, p = 0.01 for CD38; r = -0.46, p = 0.0089 for IL-6; and r = -0.5, p = 0.0042 for TNF-alpha). Additionally, the inhibitory function of Treg cells was associated with elevated expression of IL-4 (p < 0.001), IL-10 (p < 0.001), and TGF-β (p < 0.05), whereas IL-17a was not found to be involved in the suppressive activity of Treg cells. Given that monocytes and their mediators are significant factors in chronic inflammatory conditions, these results endorse the prospective application of Treg cells as an immunotherapeutic target. For people with a strong depletion of Treg cells, we suggest a Treg cell-based immunotherapy, which consists of autologous Treg cell generation from stem cells.