PRETREATMENT OF LYMPHOCYTES WITH MERCURY IN-VITRO INDUCES A RESPONSE IN T-CELLS FROM GENETICALLY-DETERMINED LOW-RESPONDERS AND A SHIFT OF THE INTERLEUKIN PROFILE

Mercury can induce autoimmune disease in susceptible mouse strains. We found that in vitro mercuric chloride induced a high proliferative re sponse in spleen lymphocytes from mercury-susceptible SJL mice, but a low response in resistant mice, such as C57BL/6 (H-2(b)), A/J (H-2(a)) and CBA (H-2(k)) mice. However, a high proliferative response was obt ained with lymphocytes from all tested low-responder mice by pretreati ng them in vitro for 1-3 days with mercuric chloride and then wash awa y the excess mercury. Both CD4(+) and CD8(+) T cells were activated in the restored response, but CD4(+) T cells was the major responding ce ll population, as in high-responder mice. We also measured the cytokin e production at the protein level after mercury stimulation in vitro. We found that in mercury stimulation the different culture conditions resulted in different patterns of cytokine production. The continuous presence of mercury induced interleukin-2 (IL-2) and interferon-gamma, but not IL-4 production in spleen cells from both high- and low-respo nder mice. In contrast, by pretreating the cells with mercury and then washing, spleen cells from both high and low-responder mice produced IL-4. Our results suggest that spleen cells from both mercury-suscepti ble and -resistant mice have the potential to respond to mercury in vi tro and produce both Th1- and Th2-type cytokines. But the mercury-indu ced cytokine profile can shift depending on the conditions for activat ion.