T-CELL DIFFERENTIATION: MOLECULAR MECHANISMS

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Various aspects and models of the regulation of T-cell differentiation are addressed. Evidence is given that certain T-cell lymphoma clones are inducible to express Lyt-1 in vitro. The blocking of Lyt-1 expression and accompanying IL-2 production by Ly-5 monoclonal antibody, and other data, suggest to us that Ly-5 on pre-Lyl cells is involved in the IL-1 dependent step leading to IL-2 production and the Lyl phenotype. We aim to characterize this transition in terms of transcription and translation. We find that recombinant gamma-interferon can induce the Lyb-2 and suceeding sIg surface phenotypes of B lineage cells. A point of special interest is that this requires far less gamma-interferon than is needed in conventional virus-protection (CPE) assay. Gamma-interferon may thus deserve consideration as an agent of lymphocyte differentiation even in circumstances where ordinary CPE assay does not reveal its presence. The meaning of Lyt-1 expression by a sub-set of B cells as well as the Ly1 and Ly123 sets of T cells is obscure. We aim to elucidate the induced augmentation of Lyt-1 we observe in mitogen-stimulated clonal B cells, in terms of transcription and translation in comparison with T cells. The clonal Abelson lymphoma lines described generate a predominant B population expressing the 220K isoform of Ly-5 in culture but a predominant T population expressing the 200K isoform in vivo. If the notion is correct that the originating transformed cell was therefore the progenitor cell for lymphocytes, we have a valuable model of alternative differentional options (T versus B) with which to study the regulation of lineage-related isoform expression. We aim first to determine whether the alternative routes adopted by these Abelson lines in fact conform to the normal T and B lineages in terms of Ly-5 transcription and translation. With regard to the aberrant expression of a 220K (B-like) Ly-5 product which we observe in the expanding Ly1 T cell population of lpr/lpr and gld/gld mice with lympho-proliferative syndrome, we aim to settle the question of whether this 220K is indistinguishable from the 220K isoforms of normal B cells or a product peculiar to proliferating Ly1 cells, whether that proliferation is normal or abnormal. (LB)