title: Impaired th1/tc1 cytokine production of tumor-infiltrating lymphocytes in a model of primary intraocular B-cell lymphoma.
abstract: OBJECTIVE
  Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma with a pathogenesis that is still unclear. Microenvironment is known to be crucial in controlling tumor growth and maintenance. To study the immune microenvironment in intraocular lymphomas and to characterize the cytokine polarization of infiltrating T-lymphocytes, a new murine model of intraocular B-cell lymphoma was developed.
  
  
  METHODS
  Immunocompetent adult mice were injected intravitreally with a syngeneic lymphomatous B-cell line. Clinical, histologic, and flow cytometric analyses were performed to characterize the tumoral invasion and the immune infiltration. Cytokine production of ocular cells was investigated by RT-PCR and fluorescent immunoassay, with or without stimulation by anti-CD3(+) anti-CD28 antibodies.
  
  
  RESULTS
  Intraocular lymphoma developed in eyes injected by lymphomatous B-cells. At day 19, the retina and the vitreous cavity were infiltrated by tumor cells. Up to 15% of living cells were T-lymphocytes. Cytokine profile analysis of the supernatant of ocular cells cultured ex vivo demonstrated the presence of IL10, IL6, IFNgamma, and TNFalpha. Stimulation of ocular cells with anti-CD3(+) anti-CD28 antibodies increased the IFNgamma level and led to the induction of IL2 production, completing the type 1 (Th1/Tc1-like) pattern of cytokine expression observed. IL12p70 and IL4, potent Th1 or Th2 differentiating factors, were undetectable, even after stimulation.
  
  
  CONCLUSIONS
  The results suggest that T-cells from intraocular B-lymphomas are characterized by a Th1/Tc1-like profile that could be partially inhibited in vivo. These data raise the possibility of a T-cell immunostimulation to reactivate the Th1/Tc1-lymphocytes and improve intraocular antitumoral immunity.
authors.affiliation: Immune Microenvironment and Tumors Group, INSERM UMRS872, Université Pierre et Marie Curie-Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Touitou
authors.forename: Cécile
authors.initials: C
authors.lastname: Daussy
authors.forename: Bahram
authors.initials: B
authors.lastname: Bodaghi
authors.forename: Serge
authors.initials: S
authors.lastname: Camelo
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Kozak
authors.forename: Phuc
authors.initials: P
authors.lastname: Lehoang
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Naud
authors.forename: Audrey
authors.initials: A
authors.lastname: Varin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Thillaye-Goldenberg
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Béral
authors.forename: Wolf Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection; D014822:Vitreous Body / Q000473:pathology*
chemical_list: D016207:Cytokines