Regulatory role of T cells in a murine model of lymphoproliferative disease.
As NZB mice age, approximately 90% of the 12-month-old mice possess an expansion of malignant B-1 (CD5+ B cells) cells with many similarities to the human lymphoproliferative disease, chronic lymphocytic leukemia. Malignant B-1 cells derived from NZB mice produce significantly higher levels of IL-10 mRNA and protein than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for the expansion of B-1 cells. In this report, the infrequent animals which survived 18 months of age or longer were studied and compared to NZB mice at 12-14 months of age. Analysis of lymphoid subpopulations in the spleen and peritoneal cavity indicated that long-lived NZB mice had an expansion of CD8+ T cells rather than the typical B-1 expansion observed in the majority of NZB animals at 12 months of age. We established a CD8+ T cell clone from long-lived NZB mice which was cytotoxic for malignant B-1 cells of NZB origin both in vivo and in vitro. Analysis of the regulatory mechanisms preventing the development of genetically programmed age-dependent CLL in the murine system may elucidate possible avenues for therapeutic intervention in CLL.
Department of Pathology, UMDNJ-New Jersey Medical School, Newark 07103, USA. raveches@umdnj.edu
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Raveche
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Fernandes
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Ong
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Peng
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007945:Leukemia, Lymphoid / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008136:Longevity; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10; D007371:Interferon-gamma