Malignant B lymphocytes from non-Hodgkin's lymphoma induce allogeneic proliferative and cytotoxic T cell responses in primary mixed lymphocyte cultures: an important role of co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) in stimulation by tumor cells

Eur J Immunol. 1995 Dec;25(12):3332-41. doi: 10.1002/eji.1830251220.

Abstract

We analyzed the stimulating capacities of malignant B cells from non-Hodgkin's lymphomas (NHL) to induce an allogeneic response in primary mixed lymphocyte reaction (MLR). T cells purified from a single healthy donor (KS) were used to compare the responses induced by either malignant or hyperplastic cells. Malignant B cells induced strong proliferation of KS cells independently of their level of expression of adhesion molecules. The KS cells after MLR were predominantly CD3+, CD25+, HLA-DR+, Ki67+ and CD45RO+ T cells, and the CD4/CD8 ratio was heterogeneous (from 0.8 to 2.7). To investigate the role of co-stimulatory molecules CD80 and CD86 for the stimulatory capacities of B cells, the expression of both molecules was analyzed before and during the MLR. Most fresh malignant B cells were negative for CD80 and CD86, whereas co-cultured B cells expressed high levels of both molecules. This expression was crucial for T cell proliferation, since monoclonal antibodies directed against CD80 and CD86 completely abrogated the MLR. We also report that KS responding cells at the end of co-culture were able to lyse fresh B cells used as stimulator cells to different extents (from 10 to 51%), and the level of lysis was enhanced after PMA activation of the target cells. Inhibition experiments using CD8 and CD4 mAb showed that effector cells were mainly CD8+. This report is the first to describe the accessory function of human malignant B cells from NHL and their sensitivity to lysis mediated by CD8+ T cells, and suggests new strategies for the development of antitumor immunity in NHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / physiology*
  • B-Lymphocytes / immunology*
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • Binding, Competitive / immunology
  • Cell Adhesion Molecules / immunology
  • Cytotoxicity, Immunologic*
  • Female
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation*
  • Lymphocyte Culture Test, Mixed
  • Lymphoma, Non-Hodgkin / immunology*
  • Male
  • Membrane Glycoproteins / physiology*
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Cell Adhesion Molecules
  • Membrane Glycoproteins