Single-Cell Analysis of Costimulation by B Cells, Endothelial Cells, and Fibroblasts Demonstrates Heterogeneity in Responses of CD4+ Memory T Cells

Participation of blood vessel cells in human adaptive immune responses

“…Cultured human ECs from all vessel sources tested have proven to be capable of activating allogeneic resting memory CD4+ or CD8+ T cells to express activation antigens, to synthesize and secrete IL-2 and effector cytokines and to proliferate [3, 16, 38–43], but in these same assays, ECs generally cannot activate naïve T cells [10, 16, 43]. In contrast, allogeneic “professional” APCs, such as B cells, monocytes or dendritic cells (DC), can readily activate both memory and naïve T cells.…”

“…In assays with CD4+ T cells, the cultured human ECs are generally pre-treated with IFN-γ to re-induce class II MHC expression [16, 39, 41] or, alternatively, the ECs may be transduced with CIITA, the transcription factor that mediates class II MHC molecule expression in response to IFN-γ [44]. Antibodies that block interactions with MHC or costimulator molecules, especially LFA-3, reduces or completely eliminates T cell activation by allogeneic EC [10, 16, 40, 43]. The frequency of memory T cells that respond to allogeneic ECs is generally a few fold lower than that responding to allogeneic professional APCs [16], and in the case of CD8+ T cells, the size of proliferating alloreactive clones stimulated by ECs are also smaller [45].…”