Human T Cell Memory: A Dynamic View

Abstract

Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

Current best estimates for the average lifespans of mouse and human leukocytes: reviewing two decades of deuterium‐labeling experiments

“…They observed that dicentric lesions remained present for more than a decade in the naive T‐cell pool, and for less than a year in the memory T‐cell pool. Although the study was based on markers that are now considered insufficient to sort naive T cells, it was the first to demonstrate that in humans, immunological memory is maintained dynamically rather than by long‐lived cells …”

“…Although the study was based on markers that are now considered insufficient to sort naive T cells, 26 it was the first to demonstrate that in humans, immunological memory is maintained dynamically rather than by long-lived cells. 27 We now know that some of these studies may have overestimated T-cell turnover rates because diurnal variation in deuterium availability was hardly taken into account. 12 Nevertheless, the relative naive and memory turnover rates within each study -which do not suffer from these problems -unequivocally show that memory T cells in the blood are shorter lived than their naive counterparts.…”

“…We therefore conclude that on average, circulating memory T cells have a life-expectancy of months rather than weeks or years, again suggesting that long-lasting T-cell memory is due to relatively short-lived memory cells that maintain themselves by cell division. 25,27 Several studies have shown that the lifespan of memory T cells is remarkably similar between young and old individuals. 23,33…”

Identification of B‐ and T‐cell epitopes on HtrA protein of Orientia tsutsugamushi

“…27 An obligate intracellular microbe such as O. tsutsugamushi would need a combination of antibodies and cellmediated immunity working together to confer protective immunity. Generally, it is accepted that T-cell immunity memory is long lasting.…”

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

“…Immune memory is previously considered as an exclusive property of T cells and B cells and defined as quicker and more robust responses to recurrent antigens [72]. However, accumulating evidence proved NK cell also have memory-like feature after certain modes of challenge including antigen-specific stimulation and antigen-independent activation.…”