Mycobacterium tuberculosis Culture Filtrate Protein 10-Specific Effector/Memory CD4 + and CD8 + T Cells in Tubercular Pleural Fluid, with Biased Usage of T Cell Receptor Vβ Chains

Abstract

ABSTRACT T cell-mediated immunity is critical for the control of Mycobacterium tuberculosis infection. Identifying the precise immune mechanisms that lead to control of initial M. tuberculosis infection and preventing reactivation of latent infection are crucial for combating tuberculosis. However, a detailed understanding of the role of T cells in the immune response to infection has been hindered. In addition, there are few flow cytometry studies characterizing the Vβ repertoires of T cell receptors (TCRs) at local sites of M. tuberculosis infection in adult tuberculosis. In this study, we used culture filtrate protein 10 (CFP-10) from M. tuberculosis to characterize T cells at local sites of infection. We simultaneously analyzed the correlation of the production of cytokines with TCR Vβ repertoires in CFP-10-specific CD4 + and CD8 + T cell subsets. For the first time, we demonstrate that CFP-10-specific CD4 + or CD8 + T cells from tubercular pleural fluid can produce high levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and upregulate the expression of CD107a/b on the cell surface. The CFP-10-specific cells were effector/memory cells with a CD45RO + CD62L − CCR7 − CD27 − expression profile. In addition, we found CFP-10-specific CD4 + and CD8 + T cells in tubercular pleural fluid, with biased usage of TCR Vβ9, Vβ12, or Vβ7.2. Our findings of CFP-10-specific CD4 + and CD8 + T cells in tubercular pleural fluid are critical for understanding the mechanisms of the local cellular immune response and developing more effective therapeutic interventions in cases of M. tuberculosis infection.