The tetraspanin CD151 is a T cell activation marker demarcating hyper-responsive CD8+ CD28- T cells in HIV patients (IRC7P.433)

HIV-infected patients, despite suppressive ART, exhibit signs of immune hyperactivation and premature senescence, compromising the success of long-term ART. Elucidation of the molecular mechanisms underlying immune dysfunction will be critical to develop future immuno-modulatory therapies to improve the long-term health status of HIV patients. To achieve this goal, biomarkers that resolve dysfunctional T cell populations are needed. To this end, we here demonstrate that the tetraspanin CD151 in HIV patients on ART is highly expressed on CD28 - T cells (p + CD28 - T cells responsive to CMV pp65 peptides were CD151 + as measured by Granzyme B + and IFN-γ + . Blocking experiments with CD151 mAb led to a dose-dependent reduction of IFN-γ secretion from CMV pp65- stimulated PBMCs. In summary, CD151 is elevated on senescent CD8+ CD28- T cells that demonstrate enhanced antigen-responsiveness. As prior data shows that CD151 on T cells stabilizes the immune synapse and primes T cell activation, CD151 expression may confer responsiveness of otherwise senescent T cells and present one underlying cause of immunological hyperresponsiveness in HIV patients.