Suppressed proliferative response of spleen T cells from metallothionein null mice.
To investigate the role of metal-binding protein, metallothionein (MT), in lymphocyte activation, the mitogen-induced proliferation of freshly isolated spleen cells was compared among MT-I, II null, and control 129/Sv mice. Spleen cells from MT null mice exhibited a markedly reduced proliferation compared with control cells when stimulated by concanavalin A or anti-CD3(epsilon) mAb, but not by lipopolysaccharide, indicating that only the response of T cells to mitogens was suppressed in MT null mice. Flow cytometric analysis of unstimulated spleen cells demonstrated no significant difference in the relative percentages of either B220+ and CD3+ cells or CD4+ and CD8+ cells between the two strains of mice. The production of interleukin (IL)-2 by MT null spleen cells after the stimulation by anti-CD3(epsilon) mAb was lower than that of control spleen cells, especially within 24 hr after the stimulation. The addition of IL-2 recovered the proliferation of MT null spleen cells to the control level. The reduced proliferative response to mitogenic stimulation of MT null T cells was confirmed by using purified splenic T cells. These results suggest that the MT expressed at basal level in the splenocytes plays an important role in T cell mitogen-induced proliferative response, probably by positively regulating the production of IL-2.
Mita
Masaharu
M
Laboratory Animal Research Center, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Imura
Nobumasa
N
Kumazawa
Yoshio
Y
Himeno
Seiichiro
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D007376:Interleukin-2 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D008070:Lipopolysaccharides; D003208:Concanavalin A; D008668:Metallothionein