Unresponsiveness to Con A in spleen cell cultures of M. lepraemurium-infected mice is dependent on a defective expression of high-affinity IL-2 receptors rather than on a lack of IL-2 production.
The production of interleukin-2 (IL-2) by Con A-activated spleen cells (SC) progressively declined and reached negligible values during the course of infection of C57BL/6 mice with Mycobacterium lepraemurium. In addition, the capacity of cultured SC to utilize IL-2 was highly reduced, as demonstrated by the accumulation of IL-2 activity in culture supernatants at 48 and 72 h after Con A activation. The depressed IL-2 utilization started to be observed about 1 to 2 weeks prior to the onset of the depressed IL-2 production and was not reversed by the addition of exogenous IL-2; thus implying that a lack of IL-2 utilization rather than a lack of IL-2 production could be directly responsible for the inhibition of T-cell proliferative responses to Con A in SC cultures of infected mice. The utilization of IL-2 was found to be down-regulated, at least in part, by splenic suppressor cells since, in mixed-culture experiments, SC from infected mice actively depressed the capacity of normal splenocytes to consume IL-2. Finally, the depressed IL-2 utilization would result from a 2- to 3-fold reduction of either or both the density of high-affinity IL-2 receptors and their affinity for IL-2.
Turcotte
R
R
Applied Microbiology Research Center, Université du Québec, Ville de Laval, Canada.
Lemieux
S
S
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology*; D009167:Mycobacterium lepraemurium; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003208:Concanavalin A