Characterization of functional T-cell lines derived from MRL mice

Abstract In an effort to characterize further the role of T cells in the autoimmune disease of MRL Mp - lpr lpr ( lpr ) mice, continuous cell lines were established from spleen and lymph nodes using EL-4 lymphoma supernatants as a source of T-cell growth factor(s). Five lines were derived from lpr spleen and lymph nodes, and an equal number from MRL Mp -+/+ ( +/+ ). All of the lines lost their alloreactivity after a short time in culture. Surprisingly, every line manifested marked proliferation in response to autologous irradiated spleen cells. This response was restricted to I-A k , as it was blocked with monoclonal anti-I-A k antibodies, and as B10.A(4R) accessory cells were stimulatory while B10.A(3R) were not. There was no difference in the degree of stimulation from lpr accessory cells compared to that in those from +/+ or other H-2 k mice. The T-cell lines bore Thy-1, Ly-1, L3T4, and 7D4 (interleukin 2 (IL-2) receptor), but lacked Ly-2 and surface Ig. They proliferated in response to both conventional and recombinant DNA-derived IL-2. When cocultured with Ia-identical B cells, the T-cell lines provoked B-cell division and antibody production. The cells also caused intense proliferation when cultured with freshly isolated lpr (but not +/+ ) lymph node cells. The results indicate that lpr lymphoid tissue contains functional T cells reactive to autologous la molecules and capable of inducing both B-cell activation and the proliferation of lpr lymphocytes. Such cells may be of importance in inducing hypergammaglobulinemia, autoantibody producton, and lymphoproliferation in these SLE mice.