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

Abstract:

: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.

journal_name

Eur J Immunol

authors

Martin I,Bonnefoix T,Roucard C,Perron P,Lajmanovich A,Moine A,Leroux D,Sotto JJ,Garban F

doi

10.1002/(SICI)1521-4141(199910)29:10<3188::AID-IMM

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

3188-95

issue

10

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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