T CELL DEVELOPMENT: IMMUNOGENETICS, DEFECTS, THERAPY

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Three newly characterized regulatory molecules are being studied and compared for their activity in vivo to induce (alone or in combination) the differentiation of phenotypically and functionally mature T cells in germ-free young nu/nu mice (less than three months of age). They include: (1)\a newly synthesized protease resistant TP-5 analog (corresponding to thymopoietin residues 32-36); (2) a similarly derived splenic pentapeptide, which differs from TP-5 by one amino acid substitution, but induces the phenotypic differentiation of both T and B cells in vitro; and (3) recombinant interferon-gamma, found to induce both T-\and B-cell differentiation in vitro. New comparative phenotypic and functional studies of two mutant mouse strains carrying, respectively, the unlinked gld and lpr genes that cause a similar generalized lymphoproliferative disorder and autoimmune syndrome should indicate whether the normal counterparts of the nonallelic mutant genes lpr and gld function through the same regulatory mechanism that is affected in lpr and gld homozygous mice. (LB)