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IdLNF1-specific T cell clones accelerate the production of IdLNF1 + IgG and nephritis in SNF1 mice.

We have shown that antibodies bearing a nephritogenic idiotype (IdLNF1) are important in the pathogenesis of autoimmune glomerulonephritis in the (NZB x SWR)F1 hybrid, SNF1. A significant shift in the ratio of CD4+ to CD8+ IdLNF1-specific T lymphocytes, in favour of CD4+ IdLNF1-specific T cells, occurred at 22-24 weeks of age in the SNF1 and correlated with an increase in serum IdLNF1 + IgG and its deposition in the kidney. Recently, we reported the characteristics of six IdLNF1-specific T cell clones (CD3+CD4+CD8-V beta 17a+) derived from 22-week-old SNF1 mice which proliferated in response to IdLNF1 + Ig and augmented IdLNF1 + IgG production when mixed with SNF1 B cells in vitro. No increase in the production of anti-DNA antibodies was seen. Here we report results of the adoptive transfer of three of these clones, A1, B6 and D2, into 6-8-week-old SNF1 mice. Serum immunoglobulin (Ig) (IgG and IgM) levels did not differ from those of age-matched unmanipulated SNF1 up to and including 35 days post-injection. Similarly, total IdLNF1 + Ig levels did not vary significantly among the groups until 28 days post-injection. However, elevated levels of IdLNF1 + IgG were observed as early as 7 days post-injection in mice receiving clone B6 and 21 days post-injection in mice receiving clone D2. This was in sharp contrast with the results obtained in mice treated with clone A1 or unmanipulated SNF1 mice, which did not express IdLNF1 + IgG during this period. Digital image analysis of the kidney glomeruli of mice receiving T cell clones B6 or D2 demonstrated a significantly (P < 0.05) higher level of IdLNF1 + Ig deposition and glomerulonephritis than age-matched unmanipulated SNF1 mice or mice which had received clone A1. Interestingly, there was no statistically significant difference in the production of anti-ssDNA or dsDNA antibodies with the treatments. Mean survival for mice treated with T cell clones B6 and D2 was significantly (P < or = 1 x 10(-6)) shorter compared to unmanipulated SNF1 mice, while that of mice which had received T cell clone A1 was significantly (P < or = 3 x 10(-6)) longer, as determined by chi-squared analysis. The overall survival of mice treated with clones B6 and D2 did not differ from that of unmanipulated mice; however, mice treated with clone A1 survived significantly (P < or = 0.05) longer.(ABSTRACT TRUNCATED AT 400 WORDS)