Human CD5 protects circulating tumor antigen-specific CTL from tumor-mediated activation-induced cell death.
We previously characterized several tumor-specific T cell clones from PBL and tumor-infiltrating lymphocytes of a lung cancer patient with identical TCR rearrangements and similar lytic potential, but with different antitumor response. A role of the TCR inhibitory molecule CD5 to impair reactivity of peripheral T cells against the tumor was found to be involved in this process. In this report, we demonstrate that CD5 also controls the susceptibility of specific T cells to activation-induced cell death (AICD) triggered by the tumor. Using a panel of tumor-infiltrating lymphocytes and PBL-derived clones expressing different levels of CD5, our results indicate that T lymphocyte AICD in response to the cognate tumor is inversely proportional to the surface expression level of CD5. They also suggest a direct involvement of CD5 in this process, as revealed by an increase in tumor-mediated T lymphocyte AICD following neutralization of the molecule with specific mAb. Mechanistically, our data indicate that down-regulation of FasL expression and subsequent inhibition of caspase-8 activation are involved in CD5-induced T cell survival. These results provide evidence for a role of CD5 in the fate of peripheral tumor-specific T cells and further suggest its contribution to regulate the extension of CTL response against tumor.
Friedlein
Grzegorz
G
Laboratoire "Immunologie des tumeurs humaines: Interaction effecteurs cytotoxiques-système tumoral," Institut National de la Santé et de la Recherche Médicale Unité 753, Institut Fédératif de Recherche 54, Institut Gustave Roussy, Villejuif, France.
El Hage
Faten
F
Vergnon
Isabelle
I
Richon
Catherine
C
Saulnier
Patrick
P
Lécluse
Yann
Y
Caignard
Anne
A
Boumsell
Laurence
L
Bismuth
Georges
G
Chouaib
Salem
S
Mami-Chouaib
Fathia
F
D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D061945:Caspase Inhibitors; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology*; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm; D018956:CD5 Antigens; D061945:Caspase Inhibitors; D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; D053181:Caspase 8