The origin of diversity: studying the evolution of multi-faceted CD8+ T cell responses

Abstract

During the past two decades of research in T cell biology, an increasing number of distinct T cell subsets arising during the transition from naïve to antigen-experienced T cells have been identified. Recently, it has been appreciated that, in different experimental settings, distinct T cell subsets can be generated in parallel within the same immune response. While signals driving a single ''lineage'' path of T cell differentiation are becoming increasingly clear, it remains largely enigmatic how the phenotypic and functional diversification creating a multi-faceted T cell response is achieved. Here, we review current literature indicating that diversification is a stable trait of CD8 ? T cell responses. We showcase novel technologies providing deeper insights into the process of diversification among the descendants of individual T cells, and introduce two models that emphasize either intrinsic noise or extrinsic signals as driving forces behind the diversification of single cellderived T cell progeny populations in vivo.

CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

“…This subset of CTLs expresses lower levels of GrB and perforin than other subsets but is more likely to participate in adaptive immune responses through a variety of proinflammatory cytokines, such as IFN- γ , IL-4, IL-17 and TNF-α. At present, it is believed that effector CD8 + T lymphocytes can be mainly divided into Tc1, Tc2, Tc9, Tc17, follicular cytotoxic T (Tfc), follicular helper T (CD8 + Tfh) and regulatory T (CD8 + Treg) cells in response to different stimuli, such as tumors, viral infections, allergies, autoimmune diseases and transplantation ( 17 , 18 ) ( Table 1 ).…”

Heterogeneity in the Differentiation and Function of CD8+ T Cells

“…T cells respond with strong proliferation and rapid conversion into effector cells upon re-exposure to the cognate antigen (Kaech and Cui 2012;Shrikant et al 2010). The models for generation of different subpopulations of memory Tc1 cells have been reviewed in detail recently (Buchholz et al 2012;Kaech and Cui 2012;Restifo and Gattinoni 2013).…”

T Cell Fate at the Single-Cell Level

“…However, epitope-specific T cells present during the memory phase, i.e., after the end of contraction, are not only increased in numbers but also display functional characteristics, such as distinct migratory patterns (9,10) or immediate effector cytokine production upon TCR triggering (11,12), that clearly set them apart from their naive counterparts, thereby contributing to enhanced recall immunity in a qualitative manner. For many years it has been realized that both during the effector and during the memory phase epitope-specific T cell populations harbor substantial phenotypic and functional diversity (13,14). Furthermore, the generation of different T cell subsets during infection or in response to vaccination appears to be key for the quality of antigen-specific immunity (15)(16)(17)(18).…”