Autotumour reactive T‐cell clones among tumour‐infiltrating T lymphocytes in B‐cell non‐Hodgkin's lymphomas

Abstract

Seventy-three T-cell clones (TCC) were established from tumour-infiltrating lymphocytes-T (TIL-T) derived from lymph nodes involved by B-cell non-Hodgkin's lymphomas (B-NHL) in nine patients with different histological subtypes and clinical stages. 40 TCC (55%) expressed the CD25 Ag and were also able to proliferate in the presence of irradiated autologous B-NHL cells. Among them, 23 autotumour (AuTu) proliferative TCC were found not to proliferate to autologous EBV-transformed B-cell lines, indicating that the proliferative reactivity of these TCC was preferentially directed at autologous B-NHL cells. Tested against autologous B-NHL cells, only three AuTu proliferative TCC (CD8+) showed a significant level of cytotoxicity (specific lysis > 15%). In blocking experiments, the AuTu proliferative reactivity of three TCC from one patient was strongly inhibited by anti-DR and anti-DQ mAbs, whereas that of three TCC from another patient was not affected by either anti-MHC class I or class II (DR, DP, DQ) mAbs. These findings suggest that the recognition of autologous B-NHL cells by AuTu proliferative TCC may occur through MHC-restricted as well as MHC-unrestricted mechanisms.

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

“…We previously reported that down-modulation of TCR-CD3 complexes on TCC before interaction with B-NHL or physical separation by Millipore membrane of both cell types resulted in neither activation nor expansion of TCC in response to malignant cells. These results demonstrate the necessity for cell-cell contact to induce activation of specific TCC and it is likely that TCR-HLA interactions were involved [2].…”

“…The present study describes an autologous model derived from a follicular lymphoma biopsy developed to investigate the subsequent action of CD4 + T lymphocytes on tumoral B lymphocytes and therefore their role in B lymphoma development. Anti-tumoral CD4 + TCC derived from the intratumoral infiltrating T lymphocytes were obtained as previously described [2] and four clones were randomly selected. By use of non irradiated freshly isolated B-NHL cells, our model allowed not only cognate contact between B-NHL and CD4 + TCC but preserved signaling and subsequent response (such as cytokine production and cell surface expression of costimulatory and other molecules) in B lymphocytes.…”

“…TCC were obtained as previously described [2]. To preserve the co-stimulatory factors for optimal T cell activation (cytokine release, surface expression of costimulators), non-irradiated B-NHL cells were used as feeders in the cloning procedure.…”

“…WT31 mAb against TCR § / g was purchased from Becton Dickinson (San Jose, CA). B-NHL cells and TIL-T were obtained as previously described [2]. Briefly, purification was carried out by neg-ative depletion with magnetic beads (Immunotech France) according to the manufacturer's instruction.…”

“…Until now, most investigations have focused on the role of CD8 + CTL in B lymphomas [1][2][3][4][5]. We and others have described a specific cytotoxic effect directed against the malignant cells in an autologous system, ranging from 10 % [2] to 35 % [1].…”