A Key Role for Altered Dendritic Cell Functioning in the Impaired Immunity Seen in Aged Individuals
Reginald M. Gorczynski, Munevver Sarygul, Mehtop Ulker, Thierry Waelli and Ender Terzioglu
Affiliation: University Health Network, RM 2-805, MaRS Tower, 101 College Street, Toronto, ON, M5G1L7, Canada.
It has been recognized for some time that there is a significant decline in multiple facets of immune functioning with age. Prominent amongst these are changes in the T-cell mediated arm of the immune response, with altered numbers and subsets of cells recorded; and a general preponderance of activated (“effete”) memory T cells; and a relatively impaired ability to generate novel immune responses to newly encountered antigens. Subtle changes in both the B cell arm of the immune response, and of the numbers/function of other cells belonging to the innate immune system (macrophages, mast cells, neutrophils etc) are also reported. Given the importance to normal immunity of cytokines (molecules produced by cells of the immune system which are used to communicate both within the immune system itself and with other physiological systems in the body) it is not surprising to find that there is also a growing body of data to support the hypothesis that altered cytokine production, either qualitative and/or quantitative, may help explain age-related changes in immune function. We have been intrigued by the more recent data suggesting that altered immune functioning in aged individuals may reflect an imbalance in the natural (homeostatic) cellular regulatory arm of the immune system. There is a wealth of data suggesting that regulatory T cells (Treg) exist as multiple independent cell populations in normal healthy individuals, and that their altered functioning may control susceptibility to autoimmune disease, cancer, transplant rejection, infection, allergy, and even fetal loss. Development of Treg is under “tight” control by populations of dendritic cells (DCs) which control their development/activation. Accordingly we hypothesize that the most significant perturbation in the aged immune system may reside in altered development of DCs (numbers and/or function) which in turn could impair Treg development and have profound consequences to the immune system as a whole.
Keywords: Dendritic Cell, Aged Individuals, T cells, immune system, cytokines
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