Towards a Better Understanding of CD4+ T Cells in Immune Aging
The immune system is enormously complex, and one can subdivide its cell populations near endlessly via many different combinations of characteristics, most commonly the type and amount of cell surface markers. Immune cell populations change in number and behavior with age, but which of these changes are important and which are only side-effects in the age-related decline of function and growing inflammation of the immune system? As an example of the state of present knowledge, one might look at this open access paper, in which the authors review what is known of T helper cells a population of T cells that displays the CD4 surface marker. This population is diverse in function and behavior; it can be further subdivided in many ways. As for the immune system more generally, its contributions to health, disease, and aging are only partially understood.
CD4+T cells play a notable role in immune protection at different stages of life. As individuals age, significant alterations occur in the internal and external milieu of CD4+T cells. These changes encompass reduced naive CD4+T cell (CD4+TN) levels, thymic hypofunction, peripheral mechanism regulation, untimely quiescent withdrawal, and persistent environmental antigen stimulation. The interplay between the in vivo microenvironment and the aging immune system is intricately linked, resulting in a decline in effector CD4+ T cell (CD4+Teff) proliferation capacity, alterations in differentiation patterns, imbalances in the ratio of type 1 T helper cell (Th1) to type 2 T helper cell (Th2), changes in the ratio of type 17 T helper cells (Th17) to regulatory T cells (Treg), among others. Repeated antigenic stimulation, accelerated homeostasis, and delayed clearance lead to impaired mitochondrial respiration, reduced functionality, accumulation of memory subpopulations with autophagy deficits, loss of CD27 and CD28 surface molecule expression, increased production of cytotoxic molecules, and elevated levels of terminally differentiated CD4+T cells (CD4+TEMRA).
Enhancing the function of CD4+T cell phenotype and targeted depletion thereof represents a crucial approach for improving the immune microenvironment in elderly individuals. Future exploration can focus on the mitochondrial dysfunction, metabolic reprogramming, genetic and epigenetic changes, protein homeostasis imbalance, autophagy defects, loss of cellular plasticity, and reduction of T cell receptor (TCR) pool in aging CD4+T cells to clarify the nature of changes in different subtypes of CD4+T cells under immune aging. More attention should be paid to mutual influence and interaction in the process of CD4+T cell aging, which are necessary to reverse both multi-organ senescence and immune senescence. It is evident that CD4+T cells serve as the central hub, not only influencing other immune cell populations but also orchestrating changes within internal subsets and related signaling pathways.