T cell responses: naïve to memory and everything in between

Abstract

THE MAMMALIAN IMMUNE SYSTEM can be broadly divided into two main arms: innate and adaptive immunity. As its name implies, the cells and receptors of the innate immune system are critical for the rapid recognition of the infectious agent and initiating a proinflammatory response. While the inflammation generated by innate immune cells [neutrophils, macrophages, monocytes, natural killer (NK) cells, dendritic cells (DCs), etc.] is important in the initial containment of the infection, it also informs and directs the expansion and differentiation of adaptive immune cells. Responding to the inflammatory environment created by the innate response, cells of the adaptive arm of the immune response (B cells, ␣␤ T cells, and ␥␦ T cells) are stimulated to expand in number (proliferate) and to differentiate into cells with a range of functions appropriate for the immunological challenge. Upon elimination of the invading pathogen, the majority of adaptive cells die and leave behind an (evergrowing) array of memory cell subsets. These memory cells offer a diversity of migratory properties and functions, collectively mediating a rapid and protective immune response upon reinfection. Thus, the major advantages of an adaptive response to the host are twofold. First, it allows the host to form an immune response that is specifically tailored to the invading pathogen. Second, it forms a pool of memory cells from these specific effectors that can last for many years, capable of protecting the host against reinfection by their rapid response. This combination of specificity and memory are the mechanistic underpinnings for the clinical success of vaccination.Critical to almost all functions of the adaptive immune response is the activation and programming of T cells from their naïve/resting state. Although there is much more to be learned, we now have a good basic understanding of the signals and cell types involved in the various stages of the T cell response initiated within the secondary lymphoid organs (SLOs). To provide a comprehensive overview, this review will summarize the T cell response broken down into three major stages: activation, differentiation, and memory formation. We will then assemble these components into a description of the anatomy of an immune response and its relationship to productive immune protection. T Cell ActivationThe primary mediator of T cell activation is the T cell receptor (TCR). Generated by recombination of genomic DNA sequences during T cell development in the thymus, each TCR is essentially unique and is responsible for the specificity of each T cell (26,79). Successful recombination of a functional TCR and emergence from the thymus results in a resting, "naïve" T cell capable mainly of migrating through the secondary lymphoid tissues (lymph nodes and spleen) and peripheral circulation but as yet incapable of producing any kind of response that could protect against infectious challenge. Producing a T cell that is capable of mediating immune protection first requires "activation" of the naïve ...

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

“…In parallel with the increase in CXCL10, the proportion of CD8 + Tm cells in splenocytes was also elevated. These results provided evidence that accelerated rejection mediated by CD8 + Tm cells is a crucial factor in re-transplantation (23)(24)(25) -, refers to Tm cells that display effector functions so that they provide rapid protection after antigen reencounter (29,30) as well as trafficking between spleen and non-lymphoid tissue. By definition, this increased propensity to activation, coupled with a shortened lag time to enter the cell cycle and acquire effector functions, allows Tm cells to quickly and robustly exert an effective recall response (31).…”

IL-21 Receptor Signaling Is Essential for Optimal CD4+ T Cell Function and Control of Mycobacterium tuberculosis Infection in Mice

“…The T cell receptor and costimulatory signals initiate proliferation of naïve T cells, but for the expansion of antigen specific T cells and their effector functions specific cytokine signals are essential (5–7). Members of the common γ-chain (γc) cytokine family, including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 are critically involved in deciding transcriptional profiles of effector T cells and the development of antigen-specific T cells (8–10). These cytokines regulate T-cell functions through transcription factors like T-bet, Eomesodermin (Eomes), Bcl-6 and Blimp-1 (11).…”

“…These cytokines regulate T-cell functions through transcription factors like T-bet, Eomesodermin (Eomes), Bcl-6 and Blimp-1 (11). Both T-bet and Eomes are critical to regulate the expression of IFN-γ, perforin, granzyme B and effector T cells responses (8, 12). …”

Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8+ memory T cells and prolongs allograft survival time

“…Although there remain controversia about the characteristics of effector and memory T cell, memory T cells in mice are distinguished as central memory T cells (T CM , CD44 high CD62L high ) and effector memory T cells (T EM , CD44 high CD62L low ) in most studies [33]. T CM refers to memory T cells with high proliferation potential, while T EM refers to memory T cells that display effector function so that they could provide protection rapidly after antigen reencounter [34,35]. The phenotype and function of memory T cell are plastic and modulated, microenvironments influence the lineage relationship of T cells which allow T cell subset phenotype conversion [36,37].…”