title: Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7.
abstract: OBJECTIVE
  Interleukin (IL) 12 is involved in the mucosal response during intestinal inflammation but its role is not fully understood. The response of human lamina propria T lymphocytes (T-LPL) to IL-12 in terms of interferon gamma (IFN-gamma) release and proliferation was investigated, exploring whether IL-15 and IL-7 cooperate with IL-12. The role of accessory molecules (CD2 and CD28) was also investigated.
  
  
  METHODS
  Unstimulated and phytohaemagglutinin preactivated T-LPL cultures were incubated with or without the initial addition of cytokines, anti-CD2 or anti-CD28 antibodies. IFN-gamma mRNA was detected by reverse transcriptase polymerase chain reaction, and protein secretion was measured by enzyme linked immunosorbent assay (ELISA).
  
  
  RESULTS
  IFN-gamma mRNA was induced in T-LPLs by IL-12 and IL-15 but not IL-7, whereas IFN-gamma was measured only in IL-12 stimulated T-LPL cultures. IL-12 induced IFN-gamma release was not abrogated by neutralising anti-IL-2 antibody or by cyclosporin A. IL-12 synergised with either anti-CD2 or anti-CD28 antibodies in inducing IFN-gamma synthesis. In preactivated T-LPLs, IL-7 enhanced IFN-gamma release induced by both IL-12 and anti-CD2, whereas IL-15 potentiated only IL-12 induced IFN-gamma synthesis. IL-12 did not induce proliferation of either unstimulated or preactivated T-LPLs and it did not enhance the CD2/CD28 stimulated T-LPL proliferative response. No transcript for IL-12 receptor beta1 subunit was detected in freshly isolated and activated T-LPLs whereas the beta2 subunit mRNA was consistently found in T-LPL samples.
  
  
  CONCLUSIONS
  IL-12 induces human T-LPLs to produce and release IFN-gamma, and IL-15 and IL-7 cooperate with IL-12 in expanding the IFN-gamma mucosal response.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro, Catanzaro, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Monteleone
authors.forename: T
authors.initials: T
authors.lastname: Parrello
authors.forename: F
authors.initials: F
authors.lastname: Luzza
authors.forename: F
authors.initials: F
authors.lastname: Pallone
mesh_terms: D018801:CD2 Antigens / Q000494:pharmacology; D018106:CD28 Antigens / Q000494:pharmacology; D002455:Cell Division; D003092:Colitis / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018801:CD2 Antigens; D018106:CD28 Antigens; D019409:Interleukin-15; D015851:Interleukin-7; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma