CD3-mediated apoptosis of human medullary thymocytes and activated peripheral T cells: Respective roles of interleukin-1, interleukin-2, interferon-γ and accessory cells

✍ Scribed by Hervé Groux; Didier Monte; Benedicte Plouvier; Andre Capron; Jean-Claude Ameisen

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 887 KB
• Volume: 23
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830230734

✦ Synopsis

Clonal deletion represents an important mechanism for the establishment of tolerance, by the elimination of autoreactive T cells. Deletion is accomplished by programmed cell death, termed apoptosis, induced by mobilization of the T cell receptor (TCR) on both thymocytes and mature T cells. The mechanism which drives T cells towards cell death or cell proliferation after TCR mobilization remains unclear.We show here that the mobilization of the CD3ITCR complex of both CD4+ and CDS+ single-positive medullary human thymocytes and human mature activated Tcells, in the absence of accessory cells, leads to an activation-induced cell death process by apoptosis. In both cases, apoptosis was associated with interferon (IFN)-y gene expression and secretion in the absence of interleukin (1L)-2 gene expression; and the addition of anti-IFN-y antibody prevented cell death. Apoptosis could also be prevented by cyclosporin A (CsA) treatment and could be re-induced by the addition of IFN-y to CsA-treated cells. Addition of IL-2 had two different effects, it prevented apoptosis and also allowed proliferation in response to CD3 monoclonal antibody. Addition of IL-1, which induces IG2 gene expression and secretion or addition of accessory cells, had the same preventive effect. These results suggest that the uncoupling of IFN-y and IL-2 gene expression following CD3/TCR mobilization initiates apoptosis of human T cells at several different stages during development and activation. We propose that co-signals provided by accessory cells allow a coupling of IL-2 gene and IFN-y gene expression, and that an essential role for IL-2 secretion in T cell activation kvolvei secretion.