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 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.
Martin
I
I
Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche and Service d'Hématologie CHU de Grenoble, Grenoble, France.
Bonnefoix
T
T
Roucard
C
C
Perron
P
P
Lajmanovich
A
A
Moine
A
A
Leroux
D
D
Sotto
J J
JJ
Garban
F
F
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002450:Cell Communication / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D018920:Coculture Techniques; D016193:G1 Phase / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D019394:Ki-67 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4