The proliferation and differentiation of hematopoietic cells is under the control of hematopoietic growth factors. A variety of cell types are capable of producing these growth factors including endothelial cells, fibroblasts, stromal cells, monocytes and lymphocytes. Growth factors stimulate both proliferation and/or differentiation of hematopoietic cells. There is substantial redundancy in the spectrum of activity of hematopoietic growth factors in that several individual factors may act on mature and immature cells of several lineages and there are several factors that have overlapping spectra of activity. During the past year we have shown that a new growth factor, stem cell factor, acts predominantly on early committed myeloid progenitors in inducing their amplification in vitro. Our goal is also to devise strategies to determine the in vivo role of particular factors in both hematopoietic and lymphoid cell differentiation. We have devised an expression vector that results in production of antisense RNA specifically in T-lymphoid cells. These antisense RNA sequences are complimentary to interleukin-3 mRNA. Our in vitro data in cultured cell lines indicate that such antisense sequences should inhibit IL3 production. We have now obtained transgenic animals that express anti-sense RNA. One construct was engineered to achieve expression preferentially in T-lymphocytes, the predominant source of IL-3 in hematopoietic tissues. A second construct was engineered to achieve antisense RNA expression ubiquitously thereby allowing us to explore the role of interleukin-3 in non-hematopoietic cell differentiation.
