» Articles » PMID: 16827897

The Fate of Effector CD8 T Cells in Vivo is Controlled by the Duration of Antigen Stimulation

Overview
Journal Immunology
Date 2006 Jul 11
PMID 16827897
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

What controls the fate of the T-cell response remains incompletely defined. Gain of effector function facilitated by costimulation has been thought to be a crucial factor in determining the outcome of the T-cell response, i.e. long-term memory in the presence of costimulation versus tolerance induction in the absence of costimulation. In this study, we show that while costimulation or cognate CD4 helps to promote the acquisition of effector function during the initial phase of the CD8 T-cell response, the fate of effector CD8 T cells is controlled by the duration of subsequent antigenic stimulation. Effector CD8 T cells differentiate into memory cells only after clearance of antigen, whereas in the presence of persistent antigen, effector CD8 T cells are tolerized. Furthermore, protective immunity against tumour cannot develop in the persisting antigen environment. These results suggest that removal of persisting antigen by other means might be a prerequisite for effective immunotherapy in cancer.

Citing Articles

Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Lin C, Levy P, Alflen A, Apriamashvili G, Ligtenberg M, Vredevoogd D Cancer Cell. 2024; 42(4):623-645.e10.

PMID: 38490212 PMC: 11003465. DOI: 10.1016/j.ccell.2024.02.016.


T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures.

Elliot T, Lecky D, Bending D Essays Biochem. 2023; 67(6):967-977.

PMID: 37386922 PMC: 10539945. DOI: 10.1042/EBC20220247.


Tumor reductive therapies and antitumor immunity.

Guo H, Tsung K Oncotarget. 2017; 8(33):55736-55749.

PMID: 28903456 PMC: 5589695. DOI: 10.18632/oncotarget.18469.


In situ vaccine, immunological memory and cancer cure.

Tsung K, Norton J Hum Vaccin Immunother. 2015; 12(1):117-9.

PMID: 26360526 PMC: 4962727. DOI: 10.1080/21645515.2015.1073427.


Allospecific CD4(+) effector memory T cells do not induce graft-versus-host disease in mice.

Zhang P, Wu J, Deoliveira D, Chao N, Chen B Biol Blood Marrow Transplant. 2012; 18(10):1488-99.

PMID: 22809867 PMC: 3443280. DOI: 10.1016/j.bbmt.2012.07.009.


References
1.
Schwartz R . Models of T cell anergy: is there a common molecular mechanism?. J Exp Med. 1996; 184(1):1-8. PMC: 2192660. DOI: 10.1084/jem.184.1.1. View

2.
Dittmer U, He H, Messer R, Schimmer S, Olbrich A, Ohlen C . Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection. Immunity. 2004; 20(3):293-303. DOI: 10.1016/s1074-7613(04)00054-8. View

3.
Morgan D, Liblau R, Scott B, Fleck S, McDevitt H, Sarvetnick N . CD8(+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol. 1996; 157(3):978-83. View

4.
Cella M, Scheidegger D, Lane P, Lanzavecchia A, Alber G . Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med. 1996; 184(2):747-52. PMC: 2192696. DOI: 10.1084/jem.184.2.747. View

5.
Yang Y, Wilson J . CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science. 1996; 273(5283):1862-4. DOI: 10.1126/science.273.5283.1862. View