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-l (CD5(+) B cells) cells with many similarit ies to the human lymphoproliferative disease, chronic lymphocytic leuk emia. Malignant B-l cells derived from NZB mice produce significantly higher levels of IL-10 mRNA and protein than normal B-l or B cells. IL -10 may act as an autocrine growth factor for the expansion of B-l cel ls. 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 o f age. Analysis of lymphoid subpopulations in the spleen and peritonea l cavity indicated that long-lived NZB mice had an expansion of CD8(+) T cells rather than the typical B-l expansion observed in the majorit y of NZB animals at 12 months of age. We established a CD8(+) T cell c lone from long-lived NZB mice which was cytotoxic for malignant B-l ce lls of NZB origin both in vivo and in vitro. Analysis of the regulator y mechanisms preventing the development of genetically programmed age- dependent CLL in the murine system may elucidate possible avenues for therapeutic intervention in CLL. (C) 1998 Academic Press.