Homotypic T-T synapses promote collective CD8(+) T cell differentiation through exchange of IFN gamma

Immunization and infection result in the differentiation of T cells, such that they acquire effector capabilities and convert into a memory pool capable of rapid response upon re-exposure. CD8 + T cells are functionally heterogeneous, but yet respond as a “whole”. During the course of an immune response, CD8 + T cells search for their cognate peptide on the surface of an APC. CD8 + T cells become activated, swarm and arrest on DCs. This results in both long-lived and dynamic “clusters” of T cells. We provide evidence that CD8 + T cells interact with each other during clustering events. CD8 + T cells form T–T synapses to exchange information. IFN gamma (IFNg) produced by CD8 + T cells during clustering is necessary for CD8 + T cell differentiation, but exogenous “soluble” IFNg did not rescue for lack of clustering. Furthermore, IFNg signalling in response to cytokines is reduced when T–T contacts were restricted, suggesting that T–T synapses are required for IFNg signalling in primed CD8 + T cells. We are now investigating the relationship between the kinetic of IFNgR expression and T cell clustering. Preliminary experiment suggests that receptor down-regulation after TCR triggering allows for T cells to become more sensitive to IFNg secreted at T–T synapse compared to IFNg secreted in the milieu. All together, we conclude that close T–T contacts provide a site for directional delivery of cytokine but also potentiate their capacity to respond, helping them mutually differentiate.