Host defence against tuberculosis infection involves T-lymphocyte mediated cellular immune responses. In this study we assessed T-cell activation by studying the early signal transduction events and production of cytokines by human CD4+ T-cells. The study constituted of five groups of subjects: (a) untreated acid fast bacilli (AFB)+ve TB patients who have not started anti-tuberculosis therapy (ATT) [New]; (b) patients who have taken ATT for two months [2T]; (c) patients who have taken ATT for six months [6T]; (d) mantoux positive healthy controls [T+ve]; (e) mantoux negative healthy controls [T−ve]. We found that mantoux positive healthy controls produced significantly higher levels of IP3, intracellular Ca2+ and presented increased PKC activity when CD4+ T-cells were stimulated with M. tuberculosis H37Rv cell lysate as compared to mantoux negative controls. Furthermore, decreased expression of CD54 (ICAM-1) and reduced [Ca2+]i were seen in TB patients as compared to T+ve healthy controls. TB patients showed significantly lower levels of IL-2 and IFNγ and higher levels of IL-4 as compared to normal healthy controls, suggesting a diminished Th1 response. Thus, the reciprocal changes in cytokines, reduced [Ca2+]i levels, and CD54 expression in patients imply phenotype shifting of Th precursors to Th2 type in TB patients.