T cell homeostatic proliferation

Definition

Target type: biologicalprocess

The non-specific expansion of T cell populations within a whole or part of an organism to reach to a total number of T cells which will then remain stable over time in the absence of an external stimulus. [GOC:mgi_curators, ISBN:0781735149]

T cell homeostatic proliferation is a fundamental process that ensures the maintenance of a stable and diverse T cell repertoire in the absence of infection. It involves the continuous production of new T cells to replace those lost through attrition or apoptosis. This process is driven by low-grade, tonic signals received by T cells in the periphery, even in the absence of specific antigen stimulation. These signals are primarily provided by self-peptide:MHC complexes presented by antigen-presenting cells (APCs) in the secondary lymphoid organs.

The process of homeostatic proliferation is tightly regulated to prevent excessive expansion of T cells and maintain immune homeostasis. It is initiated when T cells encounter low levels of self-peptide:MHC complexes, leading to weak TCR signaling. This weak signal triggers a cascade of intracellular signaling pathways, ultimately activating transcription factors like NF-κB and NFAT. These transcription factors induce the expression of genes involved in cell survival, proliferation, and differentiation.

Homeostatic proliferation typically involves the production of memory-like T cells, which exhibit enhanced survival and proliferative capacity compared to naive T cells. These memory-like cells are primed to respond rapidly to future antigen encounters. Homeostatic proliferation is crucial for maintaining a robust and diverse T cell pool, providing a reservoir of effector cells that can effectively respond to pathogens and other threats.

Key factors influencing homeostatic proliferation include:

- **Availability of self-peptide:MHC complexes**: The abundance of self-peptide:MHC complexes in the periphery determines the strength of TCR signaling and the extent of homeostatic proliferation.
- **Cytokines**: Cytokines such as IL-7 and IL-15 play a critical role in promoting T cell survival, proliferation, and differentiation during homeostatic conditions.
- **T cell receptor (TCR) affinity**: The affinity of TCR for self-peptide:MHC complexes influences the strength of TCR signaling and the rate of homeostatic proliferation.
- **Microenvironment**: The microenvironment in which T cells reside, including the presence of other cell types and the local cytokine milieu, can influence homeostatic proliferation.

Dysregulation of T cell homeostatic proliferation can lead to various pathological conditions, including autoimmune diseases and lymphoproliferative disorders. Understanding the intricate mechanisms underlying homeostatic proliferation is crucial for developing therapeutic strategies to modulate immune responses and treat diseases.'
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