A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor alpha chain-deficient mice.
Interleukin-7 (IL-7) receptor alpha chain-deficient (IL-7R alpha-/-) mice have severely depleted lymphocyte populations and thymocyte development is arrested at the double-negative (DN) stage. We show that thymocyte development in these mice can be reconstituted by the introduction of a transgenic T cell receptor (TCR), implying that one function of the IL-7R alpha chain is to initiate TCR gene rearrangement. Expression of the recombinase-activating genes RAG1 and RAG2 was greatly reduced in the IL-7R alpha-/- thymuses, and in DN thymocytes from the TCR transgenic IL-7R alpha-/- mice, but was restored in double-positive thymocytes from the TCR transgenic IL-7R alpha-/- mice. These data suggest that the IL-7R alpha chain controls RAG expression and initiation of TCR beta chain VDJ rearrangement in DN cells. In contrast, once cells have progressed beyond the DN stage of development the IL-7R alpha chain becomes no longer essential for RAG expression.
Crompton
T
T
Imperial Cancer Research Fund, London, GB. crompton@icrf.icnet.uk
Outram
S V
SV
Buckland
J
J
Owen
M J
MJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015870:Gene Expression; D015329:Gene Rearrangement, T-Lymphocyte; D006410:Hematopoiesis; D018398:Homeodomain Proteins; D015851:Interleukin-7 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D018123:Receptors, Interleukin / Q000378:metabolism*; D020395:Receptors, Interleukin-7; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; D011506:Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein