Membrane Vesicles Inhibit T Cell Activation.

utilizes multiple mechanisms to evade host immune responses, and inhibition of effector CD4 T cell responses by may contribute to immune evasion. TCR signaling is inhibited by cell envelope lipoglycans, such as lipoarabinomannan and lipomannan, but a mechanism for lipoglycans to traffic from within infected macrophages to reach T cells is unknown. In these studies, we found that membrane vesicles produced by and released from infected macrophages inhibited the activation of CD4 T cells, as indicated by reduced production of IL-2 and reduced T cell proliferation. Flow cytometry and Western blot demonstrated that lipoglycans from -derived bacterial vesicles (BVs) are transferred to T cells, where they inhibit T cell responses. Stimulation of CD4 T cells in the presence of BVs induced expression of GRAIL, a marker of T cell anergy; upon restimulation, these T cells showed reduced ability to proliferate, confirming a state of T cell anergy. Furthermore, lipoarabinomannan was associated with T cells after their incubation with infected macrophages in vitro and when T cells were isolated from lungs of -infected mice, confirming the occurrence of lipoarabinomannan trafficking to T cells in vivo. These studies demonstrate a novel mechanism for the direct regulation of CD4 T cells by lipoglycans conveyed by BVs that are produced by and released from infected macrophages. These lipoglycans are transferred to T cells to inhibit T cell responses, providing a mechanism that may promote immune evasion.