IMPROVEMENT OF TH1 FUNCTIONS DURING THE REGULATION PHASE OF MERCURY DISEASE IN BROWN-NORWAY RATS

Brown Norway (BN) rats are poor responders to T-cell mitogens and allo antigens when compared to Lewis (LEW) rats. This is dependent partly u pon a defect in IL-2 production. The TH2-mediated immune abnormalities observed in BN rats injected with mercuric chloride (HgCl2) are self- limited and it is probable that this regulation phase involves TH1-lik e cells. This paper reports on a study of the ability of lymph node ce lls (LNC) from normal BN and LEW rats and from HgCl2-injected BN rats to produce IL-2 and to proliferate when stimulated in vitro by Con A o r alloantigens in mixed lymphocyte reaction (MLR), as well as to devel op a cytotoxic T lymphocyte (CTL) response to alloantigens. This study will confirm that LNC from BN rats proliferate less than LNC from LEW rats, that the former produce less IL-2 than the latter, and that the proliferative response is restored partially after addition of IL-2. In addition, it is shown (1) that the CTL response is defective in nor mal BN rats when compared to that of normal LEW rats, and (2) that, af ter the second week of HgCl2 injections, the proliferative responses t o Con A and alloantigens are improved as well as IL-2 production, and a complete restoration of CTL function is observed. These results show that normal BN rats are deficient in the induction of TH1-like cells and that, from the second week of HgCl2 injections, these TH1 function s improve.