THE NEPHRITOGENIC T-CELL RESPONSE IN MURINE CHRONIC GRAFT-VERSUS-HOSTDISEASE

To investigate mechanisms of cell-mediated events in chronic glomerulo nephritis, T cell clones were isolated from kidneys of animals with mu rine chronic graft-vs-host disease. This systemic disorder is induced in normal (C57BL/6 x DBA2)F-1 recipients (H-2(b/d)) following transfer of parental (DBA/2) T cells (H-2(d)), These studies demonstrate that mouse renal (MR) T cells isolated from nephritic kidneys of diseased r ecipients are host-derived CD4+ alpha/beta(+) T cells. Adoptive transf er of a panel of MR clones to naive (C57BL/6 x DBAI2)F-1 recipients re veals distinct functional subsets. One subset does not transfer renal disease, and one induces severe renal inflammation and damage. In vitr o proliferative responses of nephritogenic MR clones reveal predominan t reactivity toward autologous class II MHC (I-E-d/I-A(d)) determinant s, and selected nephritogenic MR clones preferentially recognize renal Ag preparations derived from normal (C57BL/6 x DBA/2)F-1 kidneys, In addition, cytokine profile analysis of MR clones indicates a Th2 patte rn with IL-4 and IL-10 expression, although nephritogenic T cell clone s also express IFN-gamma. These data suggest that the nephritogenic T cell response in chronic graft-vs-host disease is autoreactive in natu re and may be restricted by determinants shared by both graft and host (Ia(d)).