Th1 lymphocytes are considered the main mediators of protection against tuberculosis (TB); however, their phenotypic characteristics and relationship with Th17 and Th1Th17 populations during TB are poorly understood. We have analyzed Th1, Th17, and Th1Th17 lymphocytes in the blood and pulmonary lesions of TB patients. The populations were identified based on the production of IFN-γ and/or IL-17 and the coexpression of CXCR3 (X3) and CCR6 (R6). In the blood, IL-17 and IFN-γIL-17 lymphocytes were barely detectable (median, <0.01% of CD4 lymphocytes), whereas IFN-γ lymphocytes predominated (median, 0.45%). Most IFN-γ lymphocytes (52%) were X3R6, suggesting their "nonclassical" (ex-Th17) nature. In the lungs, IL-17 and IFN-γIL-17 lymphocytes were more frequent (0.3%, < 0.005), yet IFN-γ cells predominated (11%). Phenotypically, lung CD4 cells were X3R6 The degree of differentiation of blood effector CD4 lymphocytes (evaluated based on CD62L/CD27/CD28 coexpression) increased as follows: X3R6 < X3R6 < X3R6, with X3R6 cells being largely terminally differentiated CD62LCD27CD28 cells. Lung CD4 lymphocytes were highly differentiated, recalling blood X3R6 populations. Following in vitro stimulation with anti-CD3/anti-CD28 Abs, X3R6CD4 lymphocytes converted into X3R6 and X3R6 cells. The results demonstrate that, during active TB, Th1 lymphocytes predominate in blood and lungs, document differences in X3/R6 expression by blood and lung CD4 cells, and link the pattern of X3/R6 expression with the degree of cell differentiation. These findings add to the understanding of immune mechanisms operating during TB and are relevant for the development of better strategies to control it.

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