Impaired post-transcriptional expression of interleukin-2 receptor in pokeweed mitogen-activated T cells.
The expression and role of interleukin-2/interleukin-2 receptor (IL-2/IL-2R) system in the pokeweed mitogen (PWM)-induced T cell mitogenesis was studied. In the absence of monocytes (Mo), both soluble and Sepharose-bound PWM fail to induce T cell mitogenesis even when exogenous IL-2 or IL-1 or IL-1 + IL-2 or IL-4 are also present. In the presence of Mo, PWM stimulation of T lymphocytes (highly depleted of B lymphocytes) induces as much IL-2 mRNA as phytohemagglutinin (PHA), but results in higher and persistent IL-2 levels in culture supernatants despite the concomitant T cell mitogenesis, suggesting that PWM-activated T cells do not utilize the IL-2 they produce. Confirming this notion, Mo-dependent PWM-preactivated T cells, as compared to PHA-preactivated ones: (a) failed to consume exogenous IL-2 and their mitogenic response did not increase upon exposure to exogenous IL-2; (b) exhibited very low numbers of high-affinity IL-2R; and (c) showed lower expression of IL-2R p55 and undetectable expression of IL-2R p75 on their surface. Moreover, the PWM-induced T cell mitogenesis was not inhibited by anti-IL-2 or CD25 antibodies and only partially (50%-60%) inhibited by cyclosporin A, while these treatments abrogated the PHA-induced one. PWM-activated T cells, as compared to the PHA-activated ones, exhibited as high (p55) or even higher (p75) mRNA expression of both IL-2R p55 and p75 subunits. The possibility that PWM interferes with IL-2R subunits once expressed on the T cell surface was excluded. Thus, intracellular PWM-related events are likely to impair IL-2R expression post-transcriptionally. Possible explanations for this effect and its relation with the capacity of PWM to induce T cell-dependent B cell differentiation are discussed.
de la Calle-Martín
O
O
Servei d'Immunologia, Hospital Clinic i Provincial de Barcelona, Spain.
Alberola-Ila
J
J
Engel
P
P
Inglés
J
J
Fabregat
V
V
Barceló
J J
JJ
Lozano
F
F
Gallart
T
T
D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D011043:Pokeweed Mitogens / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D007376:Interleukin-2; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016572:Cyclosporine