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Anti-CD3epsilon monoclonal antibody induces programmed cell death of thymocytes and accelerates activation-induced cell death (AICD) by apoptosis of matured or transformed T lymphocytes. However, the underlying molecular mechanism of this phenomenon is unclear. Therefore, we produced a chimera protein (termed CD8epsilon by fusing the extracellular and transmembrane domains of human CD8alpha to the intracellular domain of mouse CD3epsilon and expressed in CD8- Jurkat T cells. Stable cell lines of mutants expressing the motifs of Y170F, Y181F, and Y170F/Y181F in the CD3epsilon-ITAM were established. Experiments showed that apoptosis could be induced only in the T Jurkat cells with intact CD3epsilon intracellular domain, but not in the cells with the mutant CD8epsilon when stimulated with anti-CD8alpha monoclonal antibody. This finding indicated that a single tyrosine mutation in CD3epsilon-ITAM blocked the signal transduction, causing the cell death by apoptosis when stimulated by CD8epsilon molecule. During the apoptotic process, we showed that expressions of CD95, CD95L and Nur77 were enhanced in stimulated TJK cells but not in control cells. In addition, the high expression of Nur77 kept pace with the onset of apoptosis of T-cells mediated by CD8epsilon. We further showed that 3'-phosphatidylinositol kinase (PI3K) were not only enhanced during T cell activation, but also in the AICD process. The results suggest that PI3K/Akt is not only a cell proliferation signal, but also a potential apoptosis regulator in T lymphocytes.

A small peptide of molecular mass lower than 1,000 daltons was isolated and purified from a crude extract of calf thymus. It has been demonstrated to have the activity of increasing E-rosette formation and E-receptor expression of human and porcine T-lymphocytes with three different in vitro assays. Amino acid composition analysis showed that this peptide consists of glutamic acid, aspartic acid and glycine residues at a molecular ratio of 3:3:2. A hypothesis of a multi-factoral and multi-staged mechanism of regulation of thymocyte differentiation and maturation in the thymus is proposed.