Role of autologous CD4+ T cell clones in human B non-Hodgkin's lymphoma: aborted activation and G1 blockade induced by cell-cell contact
✍ Scribed by Isabelle Martin; Thierry Bonnefoix; Corinne Roucard; Pascal Perron; Alicia Lajmanovich; Agnès Moine; Dominique Leroux; Jean-Jacques Sotto; Frédéric Garban
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 128 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
This article describes the study of the functional relationship between auto-tumor-reactive CD4 + T cell clones (TCC) and autologous malignant B cells. 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 dilution in the presence of IL-2 and autologous non-irradiated follicular lymphoma cells as feeders. After expansion, these CD4 + TCC were co-cultured with non-irradiated autologous malignant B cells. All four TCC were activated by B lymphoma cells and proliferated, as assessed by CD25 expression and cell cycle analysis. Activation and proliferation of B lymphoma cells were studied in response to activated CD4 + T cells. Although all four TCC were able to induce B lymphoma cell activation (Ki-67 antigen induction and CD40 up-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 blocking experiment using an anti-CD4 monoclonal antibody (mAb). Since anti-CD40 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 first evidence that autologous reactive CD4 + TCC can engage follicular lymphoma B cells to enter the cell cycle and induce an aborted activation stage.