The immune responses of central and effector memory BCG-specific CD4+ T cells in BCG-vaccinated PPD+ donors were modulated by Treg cells

Most of the studies evaluating the function of tuberculosis (TB)-specific T cells were only based on the ability to produce cytokines, which may not fully reflect the function of T cells. In the present study, we confirmed that Bacille Calmette Guerin (BCG) could significantly induce cytokine production by CD4+ T cells from BCG-vaccinated PPD+ donors. In addition, CD4+ T cells were activated, divided and proliferated in response to BCG stimulation. Phenotypic analysis showed that IFN-γ+CD4+ T cells displayed CD45RA−CCR7+/−CD62L−, indicating that these CD4+ T cells were central and effector memory cells. The analysis of cytokine profiles demonstrated that most of BCG-specific BrdU+CD4+ T cells produced Th1 cytokines in response to polyclonal stimulation. In addition, we found that regulatory T cells (Treg) suppressed BCG-induced proliferation and IFN-γ production by memory CD4+ T cells. The suppressive effects of Treg on BCG-specific responses of CD4+ T cells could be partially reversed by blocking the production of IL-10. Taken together, our results demonstrated that functional central and effector memory BCG-specific CD4+ T cells could be detected based on the activation, proliferation and division of these cells, and modulated by Treg in PBMCs from BCG-vaccinated PPD+ donors.