ID(LN)F(1)-SPECIFIC T-CELL CLONES ACCELERATE THE PRODUCTION OF ID(LN)F(1)+IGG AND NEPHRITIS IN SNF1 MICE

We have shown that antibodies bearing a nephritogenic idiotype (Id(LN) F(1)) are important in the pathogenesis of autoimmune glomerulonephrit is in the (NZB x SWR)F-1 hybrid, SNF1. A significant shift in the rati o of CD4(+) to CD8(+) Id(LN)F(1)-specific T lymphocytes, in favour of CD4(+) Id(LN)F(1)-specific T cells, occurred at 22-24 weeks of age in the SNF1 and correlated with an increase in serum Id(LN)F(1) + IgG and its deposition in the kidney. Recently, we reported the characteristi cs of six Id(LN)F(1)-specific T cell clones (CD3(+)CD4(+)CD8(-)V beta 17a(+)) derived from 22-week-old SNF1 mice which proliferated in respo nse to Id(LN)F(1)+Ig and augmented Id(LN)F(1) + IgG production when mi xed with SNF1 B cells in vitro. No increase in the production of anti- DNA antibodies was seen. Here we report results of the adoptive transf er of three of these clones, A1, B6 and D2, into 6-8-week-old SNF1 mic e. Serum immunoglobulin (Ig) (IgG and IgM) levels did not differ from those of age-matched unmanipulated SNF1 up to and including 35 days po st-injection. Similarly, total Id(LN)F(1) + Ig levels did not vary sig nificantly among the groups until 28 days post-injection. However, ele vated levels of Id(LN)F(1) + IgG were observed as early as 7 days post -injection in mice receiving clone B6 and 21 days post-injection in mi ce receiving clone D2. This was in sharp contrast with the results obt ained in mice treated with clone A1 or unmanipulated SNF1 mice, which did not express Id(LN)F(1) + IgG during this period. Digital image ana lysis of the kidney glomeruli of mice receiving T cell clones B6 or D2 demonstrated a significantly (P<0.05) higher level of Id(LN)F(1) + 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 treate d with T cell clones B6 and D2 was significantly (P less than or equal to 1 x 10(-6)) shorter compared to unmanipulated SNF1 mice, while tha t of mice which had received T cell clone A1 was significantly (P less than or equal to 3 x 10(-6)) longer, as determined by chi-squared ana lysis. 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 less than or equal to 0.05) longer . These observations provide evidence for the participation of Id(LN)F (1)-specific T lymphocytes in the induction of glomulerulonephritis in the SNF1 murine model for SLE nephritis.