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  • Review Article
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Maintaining the norm: T-cell homeostasis

Key Points

  • Naive T-cell survival requires stimulation of both the T-cell receptor (TCR) — by self-peptide–MHC ligands — and cytokine receptors (especially the interleukin-7 receptor, IL-7R)

  • In lymphopaenic environments, naive T cells proliferate in response to self-peptide–MHC ligands, a process that is known as homeostatic expansion. This response also requires IL-7.

  • Competition between naive T cells for TCR ligands and/or IL-7 might normally limit homeostatic expansion and control the size of the naive T-cell pool.

  • During homeostatic expansion, naive T cells often acquire the phenotypic and functional properties of memory T cells.

  • Survival and proliferation of memory CD8+ T cells occurs in the absence of TCR–MHC interactions, but requires IL-15 (or high-dose IL-7). However, none of these factors seems to be important for CD4+ memory T-cell survival or expansion.

  • Homeostatic proliferation might contribute to autoimmune T-cell responses, but it might also be used to enhance T-cell immunity in therapeutic settings.

Abstract

The persistence of naive and memory T cells has long been of interest to immunologists, but the factors that influence the survival and homeostasis of these subsets have remained obscure. In recent years, it has become evident that the homeostasis of both naive and memory T-cell pools is highly dynamic and tightly regulated by internal stimuli, including cytokines and self-peptide–MHC ligands for the T-cell receptor. These homeostatic mechanisms might have a vital influence on the capacity of the T-cell pool to respond to both foreign and self-antigens.

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Figure 1: Main factors that influence the proliferation and survival of naive, effector and memory cells.
Figure 2: Model of how 'space' in the T-cell compartment is relevant to competition for limiting resources.

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DATABASES

Entrez

HIV-1

LocusLink

4-1BBL

B7

BCL-2

CCR7

CD4

CD8

CD25

CD28

CD40

CD44

CD45

CD69

CTLA4

FYN

γc

IFN-γ

IL-2

IL-2Rβ

IL-4

IL-6

IL-7

IL-7R

IL-9

IL-12

IL-15

IL-18

IL-21

JAK3

LCK

LKLF

PI3K

TGF-β

THY1

ζ-chain

Glossary

LYMPHOPAENIA

A lymphocyte deficiency. In this review, partial or complete lack of T cells is the crucial feature.

HOMEOSTASIS

A self-regulating process for maintaining the stability of a biological system. In the context of this review, this refers to preserving T-cell numbers over time. This might be due to 'simple' survival of T cells or to balanced proliferation and death.

γc CYTOKINES

These are cytokines for which the receptor associates with the common γ-chain (γc), which is involved in cytokine-receptor signal transduction.

GRAFT-VERSUS-HOST DISEASE

(GVHD). An allogeneic response by mature T cells that are transplanted into lymphopaenic hosts. Typically, it is studied in the context of bone-marrow transplantation into animals that have been treated with radio- or chemotherapy.

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Jameson, S. Maintaining the norm: T-cell homeostasis. Nat Rev Immunol 2, 547–556 (2002). https://doi.org/10.1038/nri853

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