No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations

We set out to detect a transcriptional signature in CD4 T cells of individuals at risk of progression to active tuberculosis. We indeed found such a signature which surprisingly could be tracked to a cell population expressing both T cell (CD3) and monocyte (CD14) markers. Imaging experiments revealed that CD3+CD14+ cells included T cell:monocyte complexes with high TCR signaling activity. Broadening our investigation beyond tuberculosis, we also found CD3+CD14+-complexes as a function of time post tetanus, diphtheria and pertussis (Tdap) vaccination and as a function of disease severity in dengue infection. These data suggest that circulating Tcell:monocyte complexes form in vivo as a result of T cells recognizing antigen presented on the monocytes, and that the conventional wisdom in flow cytometry to avoid studying cell:cell complexes should be re-visited.