Differentiation profiles of conventional and ?unconventional? Tregs and their association with dysbalance in the adrenal axis along the spectrum of HIV-TB coinfection

ANGERAMI M; SUAREZ G; VECCHIONE M; SUED O; LAUFER N; AMERI D; FABRE B; MAIDANA P; BOTTASSO O; QUIROGA MF

Los Cocos (Córdoba)

Congreso; LXI Reunión de la Sociedad Argentina de Inmunología, Los Cocos (Córdoba) 7-9 Noviembre de 2013.; 2013

Sociedad Argentina de Inmunología

Tuberculosis (TB) is the leading cause of death among people living with HIV. Homeostasis of Regulatory T cells (cTreg) CD4+CD25+FoxP3+ play a central role during infection. We showed a dysregulation of the adrenal axis in HIV-TB patients and an altered frecuency of ?unconvetional? Treg (uTreg, CD4+CD25-FoxP3+). We aimed to explore Treg subsets among the TB spectrum in HIV, i.e. HIV+, co-infected (HIV-TB), latent TB infected HIV+(HIV-TBL) individuals and healthy donors (HD). To achieve this, we evaluated the maturation status of cTreg and uTreg by CD27 and CD45RA staining, as well as the presence of other Treg markers (i.e.PD-1 and CD39), and performed correlation analysis between the obtained results and adrenal hormones plasma concentration. We found that both cTreg cells and uTreg from HIV-TB had similar memory subsets distributions with lowerpercentages of Naive cells (CD27+CD45RA+) compared to HD (p<0.001). Also, increased Central Memory cells (CD27+CD45RA-) and decreased Naïve cells were seen both in cTreg and uTreg compared to their proportion in total CD4+T cells from HIV-TB (p<0.05); these similarities between cTreg and uTreg were not observed in the other groups studied. Interestingly, EMRA population (CD27-CD45RA+) among uTreg showed a positivecorrelation with DHEA and DHEA-s in infected individuals (p<0.001 and p<0.01). Finally, comparing the expression of surface markers associated with Treg, statistical higher percentages of PD-1 and CD39 were found in cTreg and uTreg of HIV-TB compared with HD (p<0.05 and p<0.01). Also, the expression of CD39 negatively correlated with plasma levels of DHEA-s in cTreg and with Cortisol in uTreg. These findings suggest a common origin for uTregs and cTregs, pointing out the possibility of HIV-TB coinfection and its adrenal imbalance as the cause of this abnormal differentiation. These results guarantee further evaluation of the function of uTreg in HIV-TB.