Characteristics of T-lymphocytes infiltrating human B-cell lymphomas

Abstract

Using a recently described technique for direct expansion of human T-lymphocytes isolated from small intestine biopsies, we have investigated the local cellular immune response in six patients with B-cell lymphomas of various subtypes. T-cell lines (TCL) were established by seeding tumor-infiltrating T-lymphocytes (T1TL) at limiting dilution in the presence of irradiated feeder cells in culture medium containing rIl-2 and phytohemagglutinin (PHA). About 1/50 T-cells gave rise to a TCL; they all were CD3+. The CD4/CD8 ratio was 3.8:1 before and after cloning. Of 45 TCLs analysed so far from one patient with B-cell lymphoma of the lung, 4 were cytotoxic as shown by their ability to exert lectin-dependent cytotoxicity against allogeneic target cells. Of these, 3 demonstrated specificity for the autologous malignant B-cells. Five TCLs lysed the NK-sensitive K562 cell line in a HLA-unrestricted manner. When tested for antigen-specific proliferative activity, 4 TCLS only responded to the autologous lymphoma cells, but 5 TCLs reacted to the autoantigenic ganglioside GM1. Southern Blot analyses did not show a clonal pattern of T-cell receptor gene rearrangement within all TITL populations. The peripheral T-lymphocytes of the lymphoma patients showed a drastically reduced response to the mitogens PHA. Concanavalin A, and pokeweed mitogen. The present report demonstrates that it is possible to analyze TITL at clonal level. This technique may be the only means of investigating the specificity of the TITL and may help us to identify the relevant tumor-associated autoantigens if tumor-induced autoimmunization is indeed one of the mechanisms that control the growth of tumors and metastases.