Different nature of the proliferation defects of GLD, LPR and MEV C57BL/6 mouse lymphoid cells.
The three non-allelic gld, lpr and mev mutations in the mouse all lead to profound immunodeficiency besides a splenomegaly and a generalized autoimmunity. Spleen cells from young B6 gld, B6 lpr and B6 mev mice all display a decreased proliferative response to the T-cell mitogen concanavalin A (ConA), but the nature of the deficiency seems very different. No restoration of proliferation could be obtained by adding exogenous recombinant rIL2 to ConA-treated mev spleen cells, this lack of IL2-responsiveness suggesting a lack of (functional) IL2-receptors. In young mice of both gld and lpr strains, a B6 wild-type level of proliferation could be reached by rIl2 addition to ConA-treated spleen cells, this normal responsiveness to exogenous IL2 suggesting a normal expression of IL2-receptors. The endogenous IL2 production by ConA-treated spleen cells decreased very much with ageing in both B6 gld and B6 lpr mice. Yet, IL2 production in young mice revealed an earlier deficiency of the B6 lpr mice: the young B6 gld IL2 levels reached about 60% of age-matched B6 wild cell levels, but the B6 lpr levels reached 14% only. Finally the addition of exogenous rIL2 to ConA-pretreated cells from old B6 gld and B6 lpr mice, while enhancing the proliferative responses, could not restore the B6 wild-type levels. This suggests that, with ageing, the expression of functional IL2-receptors may become as abnormal in these gld and lpr mutants as it is from birth in the mev mutant mice.
Froidevaux
S
S
Laboratoire d'immunologie Université Louis Pasteur, Strasbourg, Illkirch, France.
Kuntz
L
L
Velin
D
D
Loor
F
F
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D007376:Interleukin-2 / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A