Dataset Information

Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

ABSTRACT: Memory T cells are critical for vaccines and T-cell-based therapies. However, the differentiation path of memory T cells is not completely understood. Early bulk cell population-based studies support a linear model, in which effector T cells lose the effector program and dedifferentiate into memory T cells. Recent research supports a bifurcation model, where T cells choose one of the two paths, either the effector or the memory path, at an early stage of T cell responses. Terminal effector T cells lose the capacity to become memory T cells. Here, we first demonstrate that the expression of granzyme A is largely distinct from that of granzyme B and marks terminal cytotoxic effector CD8+ T cells with reduced polyfunctionality. Using a granzyme A-fate mapping mouse line and an acute viral infection model, we discovered that early memory T cells are largely derived from cells lacking a history of granzyme A expression, supporting the bifurcation model. Progressively, granzyme A-expressing terminal effector T cells dedifferentiate into functional long-term memory T cells. At the late memory phase, memory T cells are a mixed population composed of cells with different differentiation paths (i.e., the linear and the bifurcated paths) that coordinate to provide balanced immune protection.

ORGANISM(S): Mus musculus

PROVIDER: GSE336218 | GEO | 2026/06/27

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation Experiment Overall Design: An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study we provide a comprehensive phenotypic, functional and genomic profiling of terminal effectors and memory precursors, towards better understanding the generation of these subsets. The two effector subsets were FACS purified during the early expansion phase (Days 4-5 post-infection) and extensively analyzed for their phenotypic (eg. CD127, CD62L, CD27, Bcl-2, Granzyme B, etc.) and functional properties (cytokine production, cytotoxicity, homeostatic proliferation, recall proliferation), and gene expression profiles (by genome-wide microarray analyses). Mechanistic studies involving the extent of proliferation and duration of antigen stimulation on memory differentiation potential of effectors were also performed using adoptive transfer techniques.

Dataset Information

Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets