Antigen Presentation between T Cells Drives Th17 Polarization Under Conditions of Limiting Antigen

T cells form immunological synapses with professional antigen presenting cells (APCs) resulting not only in T cell activation but also in the acquisition of peptide antigen-MHC (pMHC) complexes from the plasma membrane of the APC becoming APCs themselves. We have investigated the functional outcome of T-T cell antigen presentation by CD4 T cells and found that the antigen-presenting T cells (Tpres) predominantly differentiate into regulatory T cells (Treg), whereas T cells that have been stimulated by Tpres cells predominantly differentiate into Th17 pro-inflammatory cells. Using mice deficient in pMHC uptake by T cells, we show that T-T antigen presentation is important for the development of experimental autoimmune encephalitis and Th17 cell differentiation in vivo. By varying the professional APC:T cell ratio we can modulate Treg versus Th17 differentiation in vitro and in vivo, suggesting that T-T antigen presentation underlies proinflammatory responses in conditions of antigen scarcity.