Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL

Alexander-Miller, M. A., Leggatt, G. R., Sarin, A. and Berzofsky, J. A. (1996) Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL. Journal of Experimental Medicine, 184 2: 485-492. doi:10.1084/jem.184.2.485

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Author Alexander-Miller, M. A.
Leggatt, G. R.
Sarin, A.
Berzofsky, J. A.
Title Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 1996-08
Sub-type Article (original research)
DOI 10.1084/jem.184.2.485
Open Access Status File (Publisher version)
Volume 184
Issue 2
Start page 485
End page 492
Total pages 8
Language eng
Abstract Experimental data suggest that negative selection of thymocytes can occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether, such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+ effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-α release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition can be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8+ CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell.
Keyword CYTO-TOXIC LYMPHOCYTES
PROGRAMMED CELL-DEATH
SYNTHETIC PEPTIDES
COGNATE PEPTIDES
RECEPTOR
ACTIVATION
DELETION
PROLIFERATION
TOLERANCE
INVIVO
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Wed, 09 Mar 2011, 13:00:12 EST