Immunopathological signs in mice treated with mercury compounds--I. Identification by the popliteal lymph node assay of responder and nonresponder strains.

In the present study we screened mice from 22 different inbred strains for potential differences in their immunological reaction to HgCl2. As a rapid screening test, we used the popliteal lymph node assay (PLNA). Mice were injected s.c. into one hind footpad with 3-60 micrograms of Hg2+, given as HgCl2 in phosphate-buffered saline (PBS); contralateral hindfeet remained uninjected. Control mice received PBS alone. On day 6 the weights of the draining and contralateral PLN were determined and the PLN index calculated. While we found linear dose-response curves in some strains, these curves had a different shape in others. Out of the total of 21 euthymic strains tested only strain DBA/2 (H-2d) proved to be a nonresponder to HgCl2; it remained a nonresponder over the whole dose range (3-180 micrograms Hg2+) and period of time (days 2-12) studied. The other H-2d strains tested, i.e. NZB, BALB/c and B10.D2/n, showed absent or low PLN responses only in the lower dose range (3-30 micrograms Hg2+). F1 hybrids of strain DBA/2 and the responder strain C57BL/6 gave an intermediate response. While C3H nu/nu mice failed to respond to HgCl2, C3H +/nu mice did. The weight increase of the draining PLN after HgCl2 injection was preceded in time by an increased 3H thymidine uptake by the PLN. Histologically, enlarged PLNs revealed increased cellularity in both the T-cell and the B-cell areas. When CH3HgCl, instead of HgCl2, was injected all three strains tested, including DBA/2, responded by PLN enlargement. We conclude that (1) HgCl2 is an immunostimulatory agent in mice in that it induces T-cell-dependent enlargement of the draining PLN upon local injection, (2) there are striking genetic differences between inbred strains of mice in the PLN response to HgCl2, but these differences are not paralleled by similar differences in the response to CH3HgCl, (3) responsiveness to HgCl2 appears to be inherited in a codominant fashion, and (4) there is suggestive evidence that the observed genetic differences are determined by both H-2 and non-H-2 genes.