title: Interleukin-7 supports survival of T-cell receptor-β-expressing CD4(-) CD8(-) double-negative thymocytes.
abstract: Among the milestones that occur during T-cell development in the thymus is the expression of T-cell receptor-β (TCR-β) and the formation of the pre-TCR complex. Signals emanating from the pre-TCR trigger survival, proliferation and differentiation of T-cell precursors. Although the pre-TCR is essential for these cell outcomes, other receptors, such as Notch and CXCR4, also contribute. Whether interleukin-7 (IL-7) participates in promoting the survival or proliferation of pre-TCR-expressing cells is controversial. We used in vitro and in vivo models of T-cell development to examine the function of IL-7 in TCR-β-expressing thymocytes. Culturing TCR-β-expressing CD4(-) CD8(-) double-negative thymocytes in an in vitro model of T-cell development revealed that IL-7 reduced the frequency of CD4(+) CD8(+) double-positive thymocytes at the time of harvest. The mechanism for this change in the percentage of double-positive cells was that IL-7 promoted the survival of thymocytes that had not yet differentiated. By preserving the double-negative population, IL-7 reduced the frequency of double-positive thymocytes. Interleukin-7 was not required for proliferation in the in vitro system. To follow this observation, we examined mice lacking CD127 (IL-7Rα). In addition to the known effect of CD127 deficiency on T-cell development before TCR-β expression, CD127 deficiency also impaired the development of TCR-β-expressing double-negative thymocytes. Specifically, we found that Bcl-2 expression and cell cycle progression were reduced in TCR-β-expressing double-negative thymocytes in mice lacking CD127. We conclude that IL-7 continues to function after TCR-β is expressed by promoting the survival of TCR-β-expressing double-negative thymocytes.
authors.affiliation: Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiong
authors.forename: Brooks L
authors.initials: BL
authors.lastname: Parker
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Dalheimer
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Yankee
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054504:Precursor Cells, T-Lymphoid / Q000187:drug effects / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; C576410:interleukin-7, mouse