CHARACTERIZATION OF AN INTRONLESS CD4 MINIGENE EXPRESSED IN MATURE CD4 AND CD8 T-CELLS, BUT NOT EXPRESSED IN IMMATURE THYMOCYTES

The expression of the CD4 gene undergoes a complex pattern of regulati on during T cell development, Results obtained in transgenic mice sugg est that a combination of a proximal enhancer and a silencer from the CD4 gene is sufficient to obtain a developmentally controlled expressi on along T cell maturation, We generated transgenic mice expressing th e human CD4 cDNA under the control of the human CD4 promoter and the m urine CD4 minimal proximal enhancer, No other regulatory sequences, in cluding the silencer, were included, The pattern of expression of this transgene is restricted to mature peripheral T cells, to the only mat ure heat-stable Ag (HSA)(low/-) single positive thymocytes, and to som e NK cells, Surprisingly, no expression was found in double positive o r in immature HSA(high) single positive thymocytes, These results sugg est that additional, yet uncharacterized genomic sequences are necessa ry for CD4 expression in immature thymocytes and that there is a chang e in transcription factors occurring at the late stages of T cell deve lopment, Finally, since this is the first combination of: regulatory s equences that possesses such a T mature specific pattern of expression , it should provide a novel tool to address several immunologic questi ons or for therapeutic purposes.