Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility

Abstract

Recent thymic emigrants (RTEs) are antigenically naive T cells that have recently completed intrathymic maturation and have emigrated from the thymus to the periphery. RTEs are clinically and immunologically important as they are essential for maintaining peripheral T cells in sufficient numbers in order to recognize, by their αβT-cell receptors (TCRs), a diverse array of foreign peptide antigens. However, RTE frequency and function has been poorly understood because of a lack of surface markers to distinguish them from older non-RTE naive T cells. This review summarizes the biology of the intrathymic generation and function of RTEs, including the recent identification of protein tyrosine kinase 7 (PTK7) as a novel marker for human RTEs of the CD4 (helper) T-cell lineage. PTK7+ RTEs in adults have a reduced capacity for activation-induced proliferation and cytokine production (interleukin-2 and interferon-γ) than older PTK7- naive CD4 T cells. Importantly, this immaturity in CD4 RTE effector function may contribute to the reduced adaptive immune responses observed in situations in which CD4 RTEs predominate, including the fetus, neonate and young infant, and following immune reconstitution, such as post-hematopoietic stem cell transplant. The ability to identify viable CD4+ RTEs based on PTK7 surface staining may be particularly useful in the infant for better defining the impact of nutritional and environmental factors on thymic output, peripheral T-cell function and adaptive immune responses to vaccination and infection.