Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in alpha beta T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on alpha beta T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for alpha beta T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-gamma and perforin, which are important for immune memory against TB infection. BTLA(high) alpha beta T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on alpha beta T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection.