title: IL-2 may be a limiting factor precluding lymphocytes from genetically resistant mice from responding to HgCl2.
abstract: It is unclear how HgCl2 causes autoimmune disorders in genetically predisposed rodents. We investigated the cytokine profile induced by HgCl2 in vitro, and found a high frequency of IL-2-secreting cells in splenocytes from susceptible A.SW and BALB/c mice, whereas the frequency was low in cells from resistant DBA/2 mice. More IL-2-secreting cells were induced in splenocytes from the high responder A.SW mice than in cells from the intermediate responder BALB/c mice. Unexpectedly, a similar level of IL-4 production was induced in splenocytes from BALB/c and DBA/2 mice. IL-4 production was high in unstimulated cells from A.SW mice and was further increased by HgCl2. IFN-gamma-secreting cells were detectable in splenocytes from all three strains after activation by HgCl2. The highest frequency of IL-10-secreting cells was found in splenocytes from A.SW mice after activation, whereas the frequency was lower in cells from BALB/c mice, followed by cells from DBA/2 mice. We showed that neutralizing anti-IL-2 antibody profoundly inhibited the in vitro response to HgCl2. In contrast, antibodies against IL-4, IFN-gamma and IL-10 did not significantly affect the response of splenocytes from either A.SW or DBA/2 mice. The addition of IL-2 into cultures enhanced the proliferative response to HgCl2 in splenocytes from DBA/2 mice to a level comparable with that in cells from BALB/c mice. We found no evidence for the suggestion that HgCl2 induces a Th1/Th2 imbalance in resistant/susceptible strains. We conclude that IL-2 may be a limiting factor precluding lymphocytes from resistant mice from responding to HgCl2.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects*; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013154:Spleen / Q000187:drug effects