Sj. Rozzo et al., EVIDENCE FOR POLYCLONAL T-CELL ACTIVATION IN MURINE MODELS OF SYSTEMIC LUPUS-ERYTHEMATOSUS, The Journal of immunology, 153(3), 1994, pp. 1340-1351
CD4(+) T cells have been shown to be important in the development of d
isease in murine models of SLE, We compared the TCR V beta repertoires
of young (healthy) and older (diseased) New Zealand hybrid mice as we
ll as non-autoimmune strains to characterize changes in TCR usage asso
ciated with the development of disease. Despite large increases in the
total number of splenic CD4(+) T cells with age in diseased mice, we
noted little skewing of the V beta repertoire. For example, diseased N
ZB.H2(bm12) mice failed to exhibit a significant change in the percent
age of any V beta subset despite a fivefold increase in the number of
CD4(+) T cells. Strains without lupus-like disease, including NZB.H-2(
b) mice, demonstrated no increase in CD4(+) T cell numbers with age. S
imilar to NZB. H-2(bm12) mice, (NZB x SWR)F-1 and (NZB x NZW)F-1 mice
showed disease-related increases in CD4(+) T cell numbers, but no chan
ges in V beta repertoire that could be linked to disease development.
Differences in V beta usage between young autoimmune and non-autoimmun
e strains of mice matched for either MHC or background genes were cons
istent with genetic influences unrelated to disease. Overall, the hete
rogeneous repertoire of proliferating T cells provides evidence for po
lyclonal T cell expansion in murine models of lupus and suggests that
activation either involves a multitude of conventional self-antigens o
r may be independent of the TCR. However, the requirement for specific
class II MHC molecules suggests that this polyclonal T cell expansion
is dependent on a much smaller and specific autoreactive response.