Auto-MHC Class II-Reactive T Cell Line Obtained from MRL/+ Mice Suffering from «lpr-GVHD» I.Characterization of Surface Phenotypes, Specificities and Functions in vitro

Abstract

When MRL/Mp-+/+ (MRL/+) mice are lethally irradiated and then, reconstituted with bone marrow or spleen cells from MRL/Mp-lpr/lpr (MRL/lpr) mice, they develop a graftversus-host disease (GVHD)-like syndrome, colloquially known as «lpr-GVHD».To analyze the roles of the MRL/lpr T cells in the development of «lpr-GVHD» and autoimmune diseases, several T cell lines were established from the spleen cells of MRL/+ mice suffering from «lpr-GVHD».The surface phenotypes, specificities, and functions of a representative clone (1/+ T1) of the cloned T cell lines were characterized. The l/+T1 cells showed Thy-1.2+, L3T4+ and T3+, but Lyt-2- and B220- phenotypes.Proliferative response was observed by co-culturing the cells with spleen cells from MRL/+, MRL/lpr, AKR/J, and C3H/HeN mice, but not from BALB/c or C57BL/6 mice.Furthermore, the l/+ T1 cells responded to spleen cells of B 10.BR and B 10.A but not B 10.D2 mice.The proliferative response of 1/+ T1 cells to MRL/+ spleen cells was inhibited by anti-I-E k (but not anti-I-A k or anti-K k) antibodies, suggesting that the specificity of 1/+ T1 cells is restricted to auto-MHC, in particular, I-E k.The addition of rIL-2 to the l/+T1 cell culture enhanced the proliferative response only in the presence of appropriate stimulators.Treatment of stimulator cells with J11d.2 + C (but not anti-Thy-1.2 + C or 33D1 + C) abolished the stimulatory effect, indicating that B cells are effective stimulator cells for auto-MHC class IIreactive l/+ T1 cells.When MRL/+ splenic B cells were co-cultured with 1/+ T1 cells, both B cell proliferation and IgM production were observed.In addition, IgM-class rheumatoid factor Lyt-2 + cells nor induce GVHD.In our preliminary experiments, we have found that 1/+ T1 cells have the capacity to partially convert MRL/1pr spleen cells to Lyt-2+ cells after in vitro co-culture (unpublished onservation).Further studies using 1/+ T1 cells and spleen cells from «lpr-GVHD»-suffering MRL/+ mice are in progress to clarify these points.