Effector, memory and naïve CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients

Abstract

The proportions of naïve, memory and effector CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients were studied. CD8+ T subsets were identified by using a combination of the following antibodies: anti-CD45RA, anti-CD45RO, anti-CD27 and anti-CD28, as well as antibodies to other markers. Fas-positive cells were determined in each CD8+ T subset. Also, the intracellular cytokine patterns of CD4+ and CD8+ lymphocytes from pleural effusion were analysed. In naïve, memory and effector CD8+ T subsets no significant differences were observed in peripheral blood between healthy donors and cancer patients. In contrast, a high proportion of cells with memory phenotype (CD45RA-CD45RO+CD27+CD28+) and a low proportion of cells with effector phenotype (CD45RA+CD45RO-CD27-CD28-) were found in pleural effusion with respect to peripheral blood (P<0.001). The altered proportions of CD8+ T subsets in pleural effusion were not mediated by type 2 cytokines produced by CD4+ or CD8+ lymphocytes. In the effector CD8+ T subset, from peripheral blood as well as from pleural effusion, a low percentage of perforin-expressing cells was observed compared to granzyme A-expressing cells. Additionally, a high percentage of naïve CD8+ T cells expressing Fas was found. Our data suggest that: (i) terminal-differentiation process of CD8+ T cells is blocked, and (ii) early Fas-expression in CD8+ T cells, which was reflected even in peripheral blood, may lead to apoptosis of naïve cells when they reach the effector stage. All these processes may contribute to the inadequate antitumour immune response found in lung carcinoma patients.