The tetraspanin CD151 is an activation molecule that characterizes M. tuberculosis- specific effector CD4+ T cells

Tetraspanins are a family of membrane proteins regulating cell morphology, motility, fusion, and signaling. CD151 is expressed on T cells that stabilizes the immune synapse during antigen recognition, engages in integrin signaling, and primes T cell activation. We have recently demonstrated that CD151 expression leads to increased proliferation and activation in human CD4 + T cells. Given its important functional role, we hypothesized that CD151 may be elevated on M. tb -specific effector CD4 + T cells. We assessed CD151 on ex vivo PBMCs from PPD+ donors (Purified Protein Derivative from M. tb ) stimulated with M. tb H37Rv whole cell lysate. CD151 + frequencies were elevated on IFN-γ + (52 ± 6% vs. 17 ± 2%, P + (74 ± 6% vs. 17 ± 2%, P + T cells compared to overall baseline levels. To assess the functionality of CD151 on M. tb -specific CD4 + T cells, we established an ex vivo culture model with M. tb -infected monocyte-derived macrophages (MDMs) in the presence of autologous PPD+ or PPD− donor CD4 + T cells. Upon day 6 of culture, PPD+ donor cultures, proliferating Ki67 + CD4 + T cells were elevated in CD151 and CD25, but diminished in CD57, cell surface expression. Additionally, enhanced frequencies of CD151 + Ki67 + CD4 + T cells were associated with reduced M. tb growth within autologous MDMs during ex vivo culture. In summary, CD151 is a novel T cell activation marker that is elevated on M. tb - specific CD4 + T cells, and is associated with diminished M. tb growth in culture. CD151 could thus be an interesting candidate to supplement the existing TB-TAM diagnostic (T cell activation marker of tuberculosis) – the first to assess the quality of the CD4 + effector T-cell response to M. tb – and may guide future CD4 + T-cell based vaccine strategies.