title: T-cell-rich large-B-cell lymphomas contain non-activated CD8+ cytolytic T cells, show increased tumor cell apoptosis, and have lower Bcl-2 expression than diffuse large-B-cell lymphomas.
abstract: The factor(s) responsible for the reduced B cell number and increased T cell infiltrate in T-cell-rich large-B-cell lymphomas (TCRBCLs) have not been well characterized. We studied 18 TCRBCLs and 12 diffuse large-B-cell lymphomas (DLBCLs) to compare the 1) predominant T cell subpopulation(s), 2) expression of cytotoxic granule proteins (TIA-1 and granzyme B), 3) level of tumor cell apoptosis (Apoptag system, Oncor, Gaithersburg, MD), and 4) expression of Ki-67 (Mib-1) and apoptosis-related proteins (fas (CD95), bcl-2, and p53). T cells in TCRBCLs and DLBCLs were predominantly CD8+ T cells expressing alphabeta T-cell receptors and TIA-1 (16 of 18 TCRBCLs with >50% TIA-1+ small lymphocytes) but lacking granzyme B (16 of 18 TCRBCLs with <25% granzyme B+ small lymphocytes). Scattered apoptotic tumor cells (confirmed with CD20 co-labeling) were present in 15 of 18 TCRBCLs, with 14 of 15 cases having <10% apoptotic cells. No apoptotic cells were seen in 12 of 12 DLBCLs. In 16 of 16 immunoreactive TCRBCLs, <25% tumor cells were bcl-2+, whereas 6 of 12 DLBCLs had >50% bcl-2+ tumor cells. CD95 (fas) expression was also lower, with 3 of 18 (16.7%) TCRBCLs versus 4 of 12 (33%) DLBCLs having >25% CD95+ tumor cells. TCRBCLs and DLBCLs had similar levels of p53 and Ki-67 (Mib-1) expression. Thus, T cells in TCRBCLs are non-activated cytotoxic T lymphocytes (TIA-1+, granzyme B-). Tumor cell apoptosis (perhaps cytotoxic T cell mediated) may partly account for the decreased number of large (neoplastic) B cells in TCRBCLs, but other factors (ie, decreased bcl-2 expression) may also be needed.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. raymond.felgar@gte.net
authors.forename: R E
authors.initials: RE
authors.lastname: Felgar
authors.forename: K R
authors.initials: KR
authors.lastname: Steward
authors.forename: J B
authors.initials: JB
authors.lastname: Cousar
authors.forename: W R
authors.initials: WR
authors.lastname: Macon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D053804:Granzymes; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases