In situ sensory adaptation of tumor-infiltrating T lymphocytes to peptide-MHC levels elicits strong antitumor reactivity.
We have isolated from tumor-infiltrating lymphocytes (TIL) and PBL of a lung carcinoma patient several tumor-specific T cell clones displaying similar peptide-MHC tetramer staining and expressing a unique TCR. Although these clones elicited identical functional avidity and similar cytolytic potential, only T cell clones derived from TIL efficiently lysed autologous tumor cells. Interestingly, all of these clones expressed the same T cell surface markers except for the TCR inhibitory molecule CD5, which was expressed at much lower levels in TIL than in PBL. Video-imaging recordings demonstrated that, although both T cell clones could form stable conjugates with tumor cells, the Ca(2+) response occurred in TIL clones only. Significantly, analysis of a panel of circulating clones indicated that antitumor cytolytic activity was inversely proportional to CD5 expression levels. Importantly, CD5 levels in TIL appeared to parallel the signaling intensity of the TCR/peptide-MHC interaction. Thus, in situ regulation of CD5 expression may be a strategy used by CTL to adapt their sensitivity to intratumoral peptide-MHC levels.
Dorothée
Guillaume
G
Laboratoire Cytokines et Immunologie des Tumeurs Humaines, Institut National de la Santé et de la Recherche Médicale Unité 487, Institut Fédératif de Recherche 54, Villejuif, France.
Vergnon
Isabelle
I
El Hage
Faten
F
Le Maux Chansac
Béatrice
B
Ferrand
Vincent
V
Lécluse
Yann
Y
Opolon
Paule
P
Chouaib
Salem
S
Bismuth
Georges
G
Mami-Chouaib
Fathia
F
D000222:Adaptation, Physiological / Q000276:immunology; D018956:CD5 Antigens / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D018956:CD5 Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C075784:T cell receptor Vbeta8