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Título:
Involvement of human suppressor and non-suppressor FOXP3+ T cells in HIV-1 infection
Autor/es:
ARRUVITO LOURDES; PANDOLFI JULIETA; BAZ PLÁCIDA; BILLORDO LUIS ARIEL
Lugar:
Glasgow
Reunión:
Congreso; European Congress of Immunology 2012; 2012
Institución organizadora:
EFIS
Resumen:
FOXP3 is a key transcription factor for the development and function of regulatory T cells (Tregs); however, it can also be expressed by non-suppressor T cells. In the present study, we examined the different behaviors of FOXP3+ Tregs and FOXP3+ non-Tregs in HIV-1 infected patients. # Methods: PBMCs isolated from HIV-1 infected (n=55) and healthy donors (HD, n=27) were analyzed by flow cytometry to characterize 5 subsets of CD4+ T cells: CD45RA+ FOXP3low (rTregs), CD45RA- FOXP3high (aTregs), CD45RA- FOXP3low (FOXP3+ non-Tregs), CD45RA+ FOXP3- (naïve) and CD45RA-FOXP3- (memory). Frequency and absolute number of each subset were compared and correlated with CD4 count, viral load (VL) and activation markers (HLA-DR and CD38). Moreover, in vitro susceptibility of different HD purified subset cells to HIV-1 BaL was assessed by flow cytometry and ELISA. Cytokine levels were evaluated using a multiplex approach. # Results: In addition to the absolute decrease of conventional T cells, patients present a significant decrease in all FOXP3+ T cells. aTregs from HIV-1 patients did not correlate with the CD4 count and none FOXP3+ T cells correlated with VL. Furthermore, an increase immune activation that inversely correlated with FOXP3+ non-Tregs was observed in those patients with lower CD4. We confirmed the HIV-1 infection of all CD4+ cells, presenting higher levels in aTregs, FOXP3+ non-Tregs and memory T cells. FOXP3+ non-Tregs have secreted a wide spectrum of Th1, Th2 and Th17-like cytokines in HD. Moreover, we found a dramatic decrease of Th1 and Th17-like cytokine secretion post infection of FOXP3+ non-Treg, polarizing towards a Th2 cytokine secretion. # Conclusions: In chronically infected HIV-1 patients, we found a decreased absolute number of suppressor aTregs and FOXP3+ non-Tregs. It still remains to be elucidated if the decreased number of suppressor Tregs plays a role as suppressor of the anti-viral immune response or impacts on the immunological activation phase favouring virus replication. On the other side, our results establish a new basis for the reliable characterization of the role of FOXP3+ T cells in HIV-1 individuals