Open AccessJournal Article
IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes.
TLDR
It is suggested that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.Abstract:
In recent years, several studies have confirmed the clonal elimination of thymocytes with receptors that recognize Ag and MHC molecules present on the membrane of thymic stromal cells, a process that may be relevant to the establishment of self-tolerance. In our work, we show that anti-CD3 treatment of single positive CD4+ or CD8+ human medullary thymocytes (obtained by anti-CD1a plus C) induces their apoptotic death. Some events commonly associated with the early steps of normal activation (IL-2R expression, increase in cytoplasmic Ca2+) are also induced after anti-CD3 treatment. Nevertheless, IL-2 is not secreted by these activated cells. The addition of exogenous IL-2 inhibits the apoptosis induced by anti-CD3. We suggest that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.read more
Citations
More filters
Journal ArticleDOI
Apoptosis: the biochemistry and molecular biology of programmed cell death.
TL;DR: This review first briefly covers some historical perspective on the discovery of apoptotic cell death, the characteristic morphology that accompanies this process, and the numerous cell types and mediators with which programmed cell death is associated.
Journal ArticleDOI
Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.
TL;DR: It is reported that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4- T cell death process, with the biochemical and ultrastructural features of apoptosis.
Journal ArticleDOI
Multifactorial nature of human immunodeficiency virus disease: implications for therapy
TL;DR: The immunopathogenic mechanisms underlying human immunodeficiency virus (HIV) disease are extremely complex; the disease process is multifactorial with multiple overlapping phases as mentioned in this paper, and therapeutic strategies in HIV disease must not be unidimensional, but rather must be linked to the complex pathogenic components of the disease and must address where feasible each of the recognized pathogenic processes for the possibility of therapeutic intervention.
Journal ArticleDOI
Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis
Ameisen Jc,André Capron +1 more
TL;DR: A model of AIDS pathogenesis is presented that may explain several features of HIV infection, including evolution of the disease and the development of defects in nonimmunological organs.
Journal ArticleDOI
A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death.
F. D'Adamio,Ornella Zollo,R. Moraca,Emira Ayroldi,Stefano Bruscoli,Andrea Bartoli,Lorenza Cannarile,Graziella Migliorati,Carlo Riccardi +8 more
TL;DR: GILZ expression selectively protects T cells from apoptosis induced by treatment with anti-CD3 monoclonal antibody but not by treatment of other apoptotic stimuli, and correlates with inhibition of Fas and Fas ligand expression.
References
More filters
Journal ArticleDOI
Long term culture of tumour-specific cytotoxic T cells.
Steven Gillis,Kendall A. Smith +1 more
TL;DR: An adaptation of this method which allows the long term culture of antigen-selected cytotoxic T cells which continue to demonstrate high levels of syngeneic tumour-specific cytotoxicity after more than 4 months in culture is described.
Journal ArticleDOI
Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway
Stefan Meuer,Rebecca E. Hussey,Doreen A. Cantrell,James C. Hodgdon,Stuart F. Schlossman,Kendall A. Smith,Ellis L. Reinherz +6 more
TL;DR: The findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-3-Ti receptor cross-linking.
Journal ArticleDOI
The effect of thymus environment on T cell development and tolerance
Philippa Marrack,David Lo,Ralph L. Brinster,Richard D. Palmiter,Linda C. Burkly,Richard H. Flavell,John W. Kappler +6 more
TL;DR: It is suggested that MHC molecules on thymus epithelium and bone marrow-derived cells may not be seen identically by T cell receptors.
Journal ArticleDOI
Tolerance of class I histocompatibility antigens expressed extrathymically.
TL;DR: The results point to an extrathymic mechanism of tolerance induction, dependent on the continuous presence of antigen and the lack of IL-2 in the local environment of potentially reactive T cells, in older, diabetic mice.
Journal ArticleDOI
Deletion of self-reactive T cells before entry into the thymus medulla
Hans Hengartner,Bernhard Odermatt,R Schneider,M Schreyer,G Wälle,H R MacDonald,R M Zinkernagel +6 more
TL;DR: It is shown by immunostaining of thymus cryosections and cytofluorometric analysis that Vβ6-expressing cortical T cells are present at high density in both Mlsa and Mlsb mice, but do not enter the medullary region of MLSa animals.
Related Papers (5)
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death.
J. John Cohen,Richard C. Duke +1 more