Pierre van der Bruggen
Université catholique de Louvain, Belgium
Title: A major secretory defect of human tumor-infiltrating T lymphocytes due to surface galectin impairing synapse completion
Biography
Biography: Pierre van der Bruggen
Abstract
Freshly collected human tumor-infiltrating CD8 T lymphocytes (TILs) are often defective for the secretion of cytokines and lytic enzymes. We reported previously that these functions could be restored with agents that release the galectin present at the TIL surface. We show here that the non-secreting TILs nevertheless produce normal amounts of intracellular cytokines. We observed poor LFA-1 recruitment and defective actin rearrangement at the TIL secretory synapse. These defects were relieved by galectin removal. Mild LFA-1 blockade by antibodies on normal CD8 blood T cells also blocked actin rearrangement and abolished cytokine secretion but not production. We conclude that galectin prevents the formation of a functional secretory immunological synapse by preventing optimal LFA-1 recruitment. This is the first observation of uncoupled cytokine production and secretion, a defect which is not revealed by intracellular cytokine immunomonitoring assays.