Regulatory Role of T Cells in a Murine Model of Lymphoproliferative Disease

Abstract

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 bothin vivoandin 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.