Apoptosis of alpha beta T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: its possible implications for recovery and acquired tolerance.

We have recently shown that apoptosis, an active process of cellular self-destruction, occurs in the central nervous system in Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Conventional light and electron microscopic studies suggested that some of the apoptotic cells were oligodendrocytes and that others were hematogenous mononuclear cells. To determine whether any of the apoptotic cells were T lymphocytes, we used the technique of pre-embedding immunolabelling which allows sufficient preservation of the ultrastructure to permit recognition of apoptotic changes while at the same time preserving surface antigens so that the identity of the apoptotic cells can be determined by immunocytochemistry. Light microscopic immunocytochemistry using the monoclonal antibodies OX-34 (CD2) and R73 (alpha beta T-cell receptor) revealed that 10% of the CD2+ cells and 5% of the alpha beta T lymphocytes in the parenchyma of the spinal cord were dying by apoptosis. The presence of apoptotic alpha beta T cells was confirmed by electron microscopy. About half of all the apoptotic cells within the spinal cord were labelled by these antibodies. It is possible that some of the unlabelled apoptotic cells were also T lymphocytes but that others were glial cells such as oligodendrocytes. One possible interpretation of this T-cell apoptosis is that it represents activation-induced cell death, which has recently been shown to provide a mechanism of clonal elimination of mature as well as immature autoreactive T cells. Another possible interpretation is that it is a result of corticosterone released during the course of EAE. The apoptotic elimination of target-antigen-specific lymphocytes within the target organ in this autoimmune disease may contribute to the subsidence of inflammation and, if ongoing, to the development of tolerance.