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.