Es. Sobel et al., CO-INFUSION OF NORMAL BONE-MARROW PARTIALLY CORRECTS THE GLD T-CELL DEFECT - EVIDENCE FOR AN INTRINSIC AND EXTRINSIC ROLE FOR FAS LIGAND, The Journal of immunology, 154(1), 1995, pp. 459-464
Ipr and gld mice develop systemic autoimmune diseases with nearly indi
stinguishable manifestations, including the accumulation of massive nu
mbers of CD4(-)CD8(-) T lymphocytes. In vivo chimera experiments have
shown that the Ipr mutation is functionally expressed in both T and B
cells. When lethally irradiated Ipr mice were given a combination of n
ormal and Ipr bone marrow, only Ipr-derived B cells produced autoantib
odies and only Ipr- derived T cells hyperproliferated. In contrast, an
alogous experiments with gld mice showed that the co-infuslon of norma
l bone marrow greatly reduced autoantibody production. These results i
ndicated that the gld B cell defect was extrinsic to those cells produ
cing autoantibodies, in agreement with the recent molecular data showi
ng that the normal gene products of the Ipr and gld loci form an inter
acting receptor-ligand pair. In the present study, we have extended ou
r functional studies with gld mice using T cell-marked congenic donors
. Lymphadenopathy was reduced three- to fourfold in gld mice given a c
ombination of congenic normal and gld bone marrow compared with mice g
iven gld bone marrow alone, and the absolute number of CD4(-)CD8(-) T
cells was reduced by a factor of 7. Surprisingly, the residual CD4(-)C
D8(-) T cells present in the mixed chimeras were derived entirely from
the gld donor marrow. This suggests that the gld mutation results in
both an extrinsic and intrinsic defect in T cells.