Thymic and peripheral apoptosis of antigen-specific T cells might cooperate in establishing self tolerance

Luciano D'Adamio, Katherine M. Awad, Ellis L. Reinherz

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Aside from CD4+CD8+ double-positive (DP) thymocytes, the subpopulations of T lineage cells affected by negative selection are unknown. To address whether this process occurs in more mature cell types, we have compared the responses of purified single-positive (SP) murine thymocytes and peripheral T cells to the superantigen staphylococcal enterotoxin B (SEB) utilizing as antigen-presenting cells (APC) a fibroblast cell line expressing transfected I-Ek class II molecules. Whereas ∼70% of SEB-reactive SP thymocytes, either CD4+ or CD8+, undergo programmed cell death (apoptosis) and, therefore, negative selection, CD4+ and CD8+ antigen-specific peripheral T cells are predominantly activated and proliferate to APC+SEB. Thus, mature thymocytes and peripheral T cells, with identical patterns and levels of expression of CD4, CD8 and T cell receptor (TCR), are programmed to elicit different responses following TCR stimulation. Unexpectedly, however activation of peripheral T cells was preceded by deletion of a large fraction of Vβ8+ T lymphocytes (SEB specific). This surprising phenomenon was also observed in in vivo studies: in fact, administration of SEB to adult mice resulted in depletion of the majority of antigen-specific T cells from the peripheral lymphoid tissues analyzed (lymph nodes and spleen). This depletion is the consequence of deletion as indicated by program cell death of Vβ8+ T cells and is followed by proliferation of the remaining SEB-reactive T cells. Clonal elimination of peripheral T cells may represent a mechanism by which tolerance to self antigens never expressed in and/or exported to the thymus is achieved.

Original languageEnglish (US)
Pages (from-to)747-753
Number of pages7
JournalEuropean Journal of Immunology
Volume23
Issue number3
StatePublished - Mar 1993
Externally publishedYes

Fingerprint

Self Tolerance
Apoptosis
T-Lymphocytes
Antigens
Thymocytes
Antigen-Presenting Cells
T-Cell Antigen Receptor
Cell Death
CD8 Antigens
Superantigens
CD4 Antigens
Autoantigens
Lymphoid Tissue
Thymus Gland
staphylococcal enterotoxin B
Spleen
Fibroblasts
Lymph Nodes
Cell Line

Keywords

  • Apoptosis
  • Mature thymocytes
  • Peripheral deletion
  • Staphylococcal enterotoxin B (SEB)
  • T cells

ASJC Scopus subject areas

  • Immunology

Cite this

Thymic and peripheral apoptosis of antigen-specific T cells might cooperate in establishing self tolerance. / D'Adamio, Luciano; Awad, Katherine M.; Reinherz, Ellis L.

In: European Journal of Immunology, Vol. 23, No. 3, 03.1993, p. 747-753.

Research output: Contribution to journalArticle

D'Adamio, Luciano ; Awad, Katherine M. ; Reinherz, Ellis L. / Thymic and peripheral apoptosis of antigen-specific T cells might cooperate in establishing self tolerance. In: European Journal of Immunology. 1993 ; Vol. 23, No. 3. pp. 747-753.
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