Elevated expression of prostaglandin receptor and increased release of prostaglandin E₂ maintain the survival of CD45RO⁺ T cells in the inflamed human pleural space

Throughout the body, the distribution and differentiation of T-cell subsets varies in a way that optimizes host responses. The role of activation-induced cell death (AICD) in altering the distribution of T-lymphocyte subsets at an immune or inflammatory sites has been unexplored. The objective of this study was to assess whether pleural macrophages modulate AICD of specific pleural T-lymphocyte subsets. We found that pleural T-lymphocytes spontaneously undergo apoptosis, which is associated to increased expression of both FAS and FAS ligand, to decreased expression of Bcl 2 and to caspase 8 and 3 activation. While pleural T lymphocytes were partly protected from apoptosis, autologous peripheral blood T lymphocytes increased their apoptosis when cultured with exudative pleural fluids. Pleural CD45RO⁺ T cells, in comparison to pleural CD45RA⁺ T cells, were more susceptible to apoptosis, but were preferentially protected by exudative pleural fluids. Pleural prostaglandin E 2 (PGE₂) was implicated in protecting T-lymphocytes from apoptosis because exudative pleural T lymphocytes highly express PGE₂ receptors, and because exudative pleural fluid contained high concentrations of PGE₂. Activated pleural macrophages released PGE₂ and reduced the spontaneous apoptosis of pleural T lymphocytes and depletion of PGE₂ from pleural fluids decreased this protective effect. This study demonstrates that PGE₂, released in the pleural fluids following pleural macrophage activation, prolongs the survival of specific T-cell subsets, resulting in differentiation of the T-cell repertoire within the inflamed pleural space.