title: Intratumor CD4 T-cell accumulation requires stronger priming than for expansion and lymphokine secretion.
abstract: T cells need to migrate to and accumulate inside tumors before mediating rejection of the tumor. The number of specific T cells inside tumors may depend on the efficiency of priming in the draining lymph node (DLN), intratumor deletion, suppressive phenomena, or both. We used monoclonal anti-male antigen CD4 (Marilyn) T cells and tumor cell lines expressing or not the corresponding antigen (Dby) to analyze CD4 T-cell accumulation in tumors. Priming by MHC II(+) or MHC II(-) male splenocytes or Dby(+) tumor cells induced similar Marilyn T-cell expansion in the DLN and recirculation in other lymph nodes and capacity to produce IFN-gamma. However, intratumor accumulation was different for each priming condition. In mice with Dby(-) tumors, MHC II(+) male splenocyte priming induced greater, although not statistically significant, Marilyn T-cell accumulation in the tumors than MHC II(-) male splenocyte priming. In mice with Dby(+) tumors, priming in the tumor DLN induced less Marilyn T-cell intratumor accumulation than priming by MHC II(+) male splenocytes. We saw comparable differences for Marilyn T-cell accumulation in gut lamina propria, suggesting that priming affects effector T-cell accumulation in inflamed tissues. Mature dendritic cells were loaded with graded doses of Dby peptide to control for antigen-presenting cell characteristics during priming. We observed similar proliferation, with higher concentrations inducing higher intratumor accumulation. Thus, intratumor accumulation requires stronger stimulation than for proliferation or the capacity to secrete lymphokines. In this system, priming intensity alone can explain the number of intratumor T cells without having to call for intratumor deletion or suppression phenomena.
authors.affiliation: Laboratoire d'Immunologie pré-clinique, Institut National de la Sante et de la Recherche Medicale U653, Institut Curie, Paris, France.
authors.forename: Nathalie T
authors.initials: NT
authors.lastname: Joncker
authors.forename: Julie
authors.initials: J
authors.lastname: Helft
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jacquet
authors.forename: Virginie
authors.initials: V
authors.lastname: Premel
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008222:Lymphokines; D015778:Minor Histocompatibility Antigens; D011506:Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C115600:Ddx3y protein, mouse; D053487:DEAD-box RNA Helicases