The influence of rearranged T cell receptor alpha beta transgenes on early thymocyte development.
Most murine thymocytes and mature T cells originate from a numerically minor population of CD8-4- (double-negative, DN) thymocytes. In this study, we investigated the effects of rearranged T cell receptor (TcR) alpha and beta transgenes on early T cell development. We analyzed the precursor potential, the expression of CD25 and TcR at mRNA and/or protein level in DN thymocyte subsets in TcR transgenic (Tg) mice. We report the following observations: (i) despite a large overrepresentation of total DN cells in TcR Tg mice, precursor-containing CD25+ DN and CD8lo4lo thymocytes are reduced to a third of the nontransgenic control numbers; (ii) like in the normal mice, CD25+ DN and CD8lo4lo can, and TcR+ DN cells cannot generate other thymic subsets; (iii) TcR alpha mRNA and TcR alpha/beta protein levels are quantitatively increased, but their developmental expression is similar to that in normal mice; and (iv) surface TcR alpha beta expression becomes detectable as the thymocytes down-regulate CD25, paralleling the situation in normal mice. Our findings implicate stringent transcriptional control, rather than TcR gene rearrangement, as a decisive regulator of TcR alpha beta expression in early ontogeny.
Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10021.
J
J
Nikolić-Zugić
S
S
Andjelić
H S
HS
Teh
N
N
Jain
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D005434:Flow Cytometry; D015870:Gene Expression; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta