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The Strength of Persistent Antigenic Stimulation Modulates Adaptive Tolerance in Peripheral CD4+ T Cells
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2003
- Publisher :
- Rockefeller University Press, 2003.
-
Abstract
- The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
CD4-Positive T-Lymphocytes
medicine.medical_treatment
Immunology
Antigen presentation
Receptors, Antigen, T-Cell
Cytochrome c Group
Mice, Transgenic
Stimulation
adaptation
Biology
Lymphocyte Activation
Article
anergy
Immune tolerance
F-actin
Interferon-gamma
Mice
tuning
Antigen
Antigens, CD
Immune Tolerance
medicine
Animals
Immunology and Allergy
Lectins, C-Type
IL-2 receptor
Antigens
CD69
Columbidae
Antigen Presentation
T-cell receptor
CD28
Adaptation, Physiological
Cytokine
Interleukin-2
Signal Transduction
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 198
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....2ba9b968eaf691a5041b070e57cd8bd7