Nonencephalitogenic CD4^-CD8^- Vα2Vβ8.2⁺ anti-myelin basic protein rat T lymphocytes inhibit disease induction

Recently there has been a number of reports suggesting that CD4^-CD8^- T cells participate in the processes of inflammatory reaction. In an attempt to delineate the distinctive functions of double negative (DN) T lymphocytes in an autoimmune-induced disease, we isolated and cloned such T cells, along with control CD4⁺ cells, from Lewis rats immunized with guinea-pig myelin basic protein in CFA. Both clones proliferated in response to the guinea-pig myelin basic protein and its synthetic encephalitogenic peptide, and expressed the same TCR V genes homologous to the mouse Vα2 and Vβ8.2 families that appear to be the defining entity of experimental autoimmune encephalomyelitis (EAE). Moreover, the TCR D and J region gene products of the DN cell were found to be similar to another encephalitogenic rat T cell clone. The two T clones did not differ markedly in their ability to produce TNF and IL-2 and to adhere to vascular wall-derived extracellular matrix- and laminin-coated plates. Surprising, therefore, was the finding that, although the CD4⁺ T lymphocytes were capable of inducing EAE, the DN cells did not elicit disease but rather inhibited subsequent EAE induction. Thus, TCR Vα2Vβ8.2 and its junctional region gene products are not the only prerequisite segment for a T cell to become encephalitogenic. We suggest that the important determinants of the T cell ability to induce disease are features of the T cell, other than or in addition to, the T cell receptor.