T Cells Going Innate

Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic antigen exposure, at the same time, has been shown to trigger the loss of costimulatory CD28 molecules with recently reported intensified antigen thresholds of antigen-experienced CD8+ T cells. In transplantation, NKRs have been shown to assist allograft rejection in a CD28-independent fashion. We discuss here a role for CD28-negative T cells that have acquired the competency of the NKR machinery, potentially promoting allorecognition either through T cell receptor (TCR) crossreactivity or independently from TCR recognition. Collectively, NKRs can bring about innate-like T cells by providing alternative costimulatory pathways that gain relevance in chronic inflammation, potentially leading to resistance to CD28-targeting immunosuppressants.

TrendsWhile prolonged antigen stimulation can induce the loss of costimulatory CD28 molecules, diminished TCR expression and increased antigen thresholds in antigen-experienced CD8+ T cells have been reported.Prolonged antigenic TCR-dependent activation may lead to the development of innate-like T cells that express functional NK cell receptors.Suppression of classical TCR signaling in parallel to an acquisition of NK cell receptor signaling pathways may be characteristic of innate-like T cells.CD57 can reflect the maturity of T cells and correlates with both augmented expression in addition to modified functional responsiveness of NK cell receptors in T cells.Clinically, chronic immunosuppression may promote the development of innate-like T cells by supporting infections that involve antigen exposure. Owing to their unconventional functional repertoire, innate-like T cells may escape CD28-targeting immunosuppressants.