CD4+ T cells are critical players in the immune system. CD4+ T cells coordinate both innate and adaptive immune responses. When naive CD4+ T cells become activated via their antigen-specific T cell receptor in the presence of costimulation, these cells differentiate into effector and memory T cells. Maintenance of a large and diverse naive CD4+ T cell repertoire over time is thus essential for developing immunity to a multitude of novel antigens. Despite a strong decline in thymic production of naive CD4+ T cells with aging, the circulating pool of naive CD4+ T cells is well-maintained in elderly humans. The preservation of naive CD4+ T cells in aged subjects contrasts sharply with that of naive CD8+ T cells, which decline markedly with age. In the current chapter, the mechanisms facilitating the remarkable maintenance of the naive CD4+ T cell pool with age are discussed. Important mechanisms include recognition of self-peptides by T cell receptors and stimulation by homeostatic cytokines, including interleukin-7 and interleukin-2. Furthermore, we address the implications of naive CD4+ T cell maintenance for the development of autoimmune diseases in the elderly. Lastly, two models for the development of aging-associated autoimmunity are proposed, and suggestions for further investigation are provided.
|Titel||Handbook of Immunosenescence|
|Subtitel||Basic Understanding and Clinical Implications|
|Redacteuren||Tamas Fulop, Claudio Franceschi, Katsuiku Hirokawa, Graham Pawelec|
|Uitgeverij||Springer International Publishing|
|ISBN van elektronische versie||978-3-319-64597-1|
|ISBN van geprinte versie||978-3-319-64597-1|
|Status||Published - 2018|