Abstract
CD4+ T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4+ Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4+ T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4+ tissue-resident memory T cells and of CD4+ memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4+ T cell-mediated autoimmune diseases.
Highlights
CD4+ T helper (Th) cells play a central role in the immune system and carry out multiple functions including activation, coordination, modulation, and regulation of innate and adaptive immune responses
Similar to the effector response generated by recently-activated naive T cells, the effector response of memory T cells is dependent on the nature and context of their encounter with their cognate antigen, for example provided by cues such as cytokines in the microenvironment [14]
Reinhardt et al showed that the CD4+ TCM and TEM paradigm translates to mice, and that these memory-cell subsets can be distinguished based on the expression of CD62L and CCR7 [87,93,94]
Summary
CD4+ T helper (Th) cells play a central role in the immune system and carry out multiple functions including activation, coordination, modulation, and regulation of innate and adaptive immune responses. Similar to the effector response generated by recently-activated naive T cells, the effector response of memory T cells is dependent on the nature and context of their encounter with their cognate antigen, for example provided by cues such as cytokines in the microenvironment [14]. The higher frequencies of Ag-specific memory T cells increase their likelihood to encounter their cognate antigen faster upon re-infection, and to more rapidly generate a larger effector. The unique characteristics of memory T cells enhance their ability for in situ immune surveillance, increase their likelihood for faster encounter of pathogens at the site of infection, and facilitate the generation of more rapid and generally superior effector responses
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