T CD4+CD25+ subsets in multirresistant tuberculosis (MDR-TB) patients.

GEFFNER LAURA; YOKOBORI NOEMÍ; SCHIERLOH PABLO; ALEMÁN MERCEDES; GARCÍA ANA; RITACCO VIVIANA; VESCOVO MARISA; LÓPEZ BEATRIZ; BARRERA LUCIA; ABBATE EDUARDO; SASIAIN MC; DE LA BARRERA SILVIA

Río de Janeiro

Congreso; Congreso Internacional de Inmunología; 2007

MDR-TB has been documented in Argentina in the early 90s, since then MDR Haarlem strains such as Muñiz (M, responsible for outbreaks) and 410 (that caused a single case) have been isolated. Besides, it has been demonstrated that MDR W/Beijing isolates induced IL-4 and IL-10 dependent expansion of regulatory T cells (Treg) upon stimulation of peripheral blood mononuclear cells (MC). Hence, the aim of this work was to evaluate the presence of Treg subsets in MC from patients infected with local MDR-TB strains (n=8) and PPD+ healthy donors (n=6). CD4+CD25low (25L), CD4+CD25high (25H) and CD4+ CD25+ Foxp3+ T population frequency was determined in ex vivo and 5 days cultured MC with heated H37Rv (Rv), M and 410 strains by flow cytometry. No differences in %CD4+ T cells, 25L or 25H were observed in MC ex vivo. Foxp3 expression was detected in 25H T cells. Activated CD4+ T cells (25L) were observed in both patients and healthy PPD+ upon antigen stimulation (MDR-TB: Rv=52±19%; M=72±19%; 410=54±21%; PPD+: Rv=112±81%, M=70±51%, 410=99±46%). However, an expansion of Treg (Foxp3+ CD25+) occurred in MDR-TB with M and 410 strains while not in healthy PPD+ (M: p<0.05; 410: p<0.03). Moreover, both 25H and 25L subsets from MDR-TB showed expression of IL-10. These results show that although Rv, M and 410 activate CD4+ T cells in both MDR-TB patients and PPD+ healthy donors, only M and 410 expand Treg in MDR-TB. These results indicate that acquired immunity could be modulated in MDR-TB by Mycobacterium tuberculosis strains.