Differential IL-7 responses in developing human thymocytes.
Interleukin (IL)-7 is a factor essential for mouse and human thymopoiesis. Mouse thymocytes have altered sensitivities to IL-7 at different developmental stages. CD4/CD8 double positive (DP) mouse thymocytes are shielded from the influence of IL-7 because of loss of CD127 (IL-7Ralpha). In this study, we assessed IL-7 receptor expression and IL-7 signaling in human thymocytes. We found human DP cells to be severely limited in their ability to phosphorylate STAT-5 in response to IL-7. The relative expression levels of the IL-7-inducible proteins Bcl-2 and Mcl-1 were also lower in human DP cells, consistent with a stage-specific decrease in IL-7 responsiveness. IL-7 responses were restored in a subset of cells that matured past the DP stage. Unlike the regulation of IL-7 signaling in mouse thymocytes, loss of IL-7 signaling in human DP cells was not due to absence of CD127, but instead correlated with downregulation of CD132 (common gamma chain).
Marino
Julie H
JH
Department of Surgery, University of Oklahoma College of Medicine, Tulsa, OK, USA.
Tan
Chibing
C
Taylor
Ashlee A
AA
Bentley
Caroline
C
Van De Wiele
C Justin
CJ
Ranne
Richard
R
Paliotta
Marco
M
Broughan
Thomas A
TA
Teague
T Kent
TK
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C415350:interleukin-7 receptor, alpha chain