Sl. Peng et al., PATHOGENESIS OF AUTOIMMUNITY IN ALPHA-BETA-T-CELL-DEFICIENT LUPUS-PRONE MICE, Clinical and experimental immunology, 111(1), 1998, pp. 107-116
Murine lupus in MRL mice has been strongly attributed to alpha beta T
cell-dependent mechanisms. Non-alpha beta T cell-dependent mechanisms,
such as gamma delta T cells, have been shown to drive antibody and au
toantibody production, but they have not been considered capable of in
ducing end-organ disease. Here, we have expanded upon the findings of
such previous work by examining the mechanism and extent of end-organ
disease attainable via gamma delta T cells and/or non-alpha beta T cel
l-dependent mechanisms, assessing two prototypical lupus lesions, rena
l and skin disease, in TCR alpha -/- MRL mice that possessed either fu
nctional or defective Fas antigen (Fas + or lpr). Observed to 1 year o
f age, TCR alpha -/- MRL mice developed disease characterized by incre
ased mortality, overt renal disease and skin lesions. While delayed in
onset and/or reduced in severity compared with TCR alpha +/+ MRL/lpr
animals, renal and skin lesions in alpha beta T cell-deficient animals
were clearly increased in severity compared with age-matched control
nonautoimmune mice. In contrast to TCR alpha +/+ MRL mice, whose disea
se reflected pan-isotype immune complex deposition with significant co
mplement fixation, renal disease in TCR alpha -/- MRL animals reflecte
d predominantly IgG1 immune complex deposition, with poor complement f
ixation. Thus, this study demonstrates conclusively that non-alpha bet
a T cell-dependent mechanisms can induce renal and skin injury in muri
ne lupus, but at least in the kidney, only via humoral autoimmunity of
a relatively nonpathological isotype which results in the delayed ons
et of end-organ damage.