Role of autologous CD4(+) T cell clones in human B non-Hodgkin's lymphoma:aborted activation and G1 blockade induced by cell-cell contact

This article describes the study of the functional relationship between aut o-tumor-reactive CD4(+) T cell clones (TCC) and autologous malignant B cell s. Four auto-tumor-reactive CD4(+) TCC were derived from tumor-infiltrating T lymphocytes (TIL-T) from a freshly isolated human follicular lymphoma by the following technique: total CD4(+) TIL-T were negatively purified by an immunomagnetic procedure, then CD4(+) TCC were obtained by limiting diluti on in the presence of IL-2 and autologous non-irradiated follicular lymphom a cells as feeders. After expansion, these CD4(+) TCC were co-cultured with non-irradiated autologous malignant B cells. All four TCC were activated b y B lymphoma cells and proliferated, as assessed by CD25 expression and cel l cycle analysis. Activation and proliferation of B lymphoma cells were stu died in response to activated CD4(+) T cells. Although all four TCC were ab le to induce B lymphoma cell activation (Ki-67 antigen induction and CD40 u p-regulation), cells were subsequently blocked in G1 phase. Activation of B -NHL cells was mediated by TCR-HLA class II interaction, as shown by a bloc king experiment using an anti-CD4 monoclonal antibody (mAb). Since anti-CD4 0 mAb with or without IL-4 did not induce proliferation of B lymphoma cells in contrast to normal B cells, we suggest that the blockade in G1 phase is due to the presence of abnormalities in B lymphoma cells. This is the firs t evidence that autologous reactive CD4(+) TCC can engage follicular lympho ma B cells to enter the cell cycle and induce an aborted activation stage.