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.
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.
Plumas
J
J
Immunology Laboratory, Blood Center, Grenoble, France.
Chaperot
L
L
Jacob
M C
MC
Molens
J P
JP
Giroux
C
C
Sotto
J J
JJ
Bensa
J C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D001667:Binding, Competitive / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins