title: IL-2 secretion is pertussis toxin sensitive in a T lymphocyte hybridoma.
abstract: Interaction of specific ligands with TCR initiates a cascade of biochemical events which leads to expression of high affinity IL-2R and subsequent IL-2 secretion. Activation of phospholipase C (PL-C) is considered to be a key event in the initiation of this cascade. However, in addition to this PL-C-dependent pathway, PL-C-independent pathways have been hypothesized. Identification of the steps constituting these PL-C-independent pathways has been difficult because activation of PL-C and the subsequent cascade of events mask the effects of such pathways. Specific inhibitors for PL-C, or mutants defective in, the PL-C pathway would facilitate delineation of alternative activation pathways. We have identified a murine pork insulin/IAd-specific T cell hybridoma, B8P3.11, in which perturbation of the B8P3.11 TCR by either Ag in association with Ia, anti-CD3 antibodies, or a mitogenic lectin does not induce increases in myo-inositol 1,4,5-triphosphate production or cytosolic free calcium, yet it does lead to IL-2 secretion. Treatment of B8P3.11 with pertussis toxin, at concentrations which ADP-ribosylate GTP-binding proteins, inhibits IL-2 secretion. Thus, signal transduction resulting in IL-2 secretion by B8P3.11 likely involves a G protein. In contrast, TCR/ligand interaction activates the PL-C-dependent pathway in LBRM 331A5, a T cell lymphoma. Furthermore, pertussis toxin treatment, which blocks IL-2 secretion by B8P3.11, does not alter IL-2 secretion by LBRM 331A5. However, similar pertussis toxin substrates are present in both cells. Therefore, B8P3.11 T cells should help to elucidate PL-C-independent activation pathways.
authors.affiliation: Oncology Research, Toronto General Hospital, Ontario, Canada.
authors.forename: J B
authors.initials: JB
authors.lastname: Stanley
authors.forename: R M
authors.initials: RM
authors.lastname: Gorczynski
authors.forename: T L
authors.initials: TL
authors.lastname: Delovitch
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D007295:Inositol Phosphates / Q000502:physiology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007526:Isoelectric Point; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008934:Mitogens; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007295:Inositol Phosphates; D007376:Interleukin-2; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D010741:Phospholipases A; D010738:Type C Phospholipases; D002118:Calcium