Interleukin-7 negatively regulates the development of mature T cells in fetal thymus organ cultures.
We added antibody specific for interleukin-7 (IL-7) to chimeric fetal thymus organ cultures (FTOC) to investigate the involvement of this cytokine at distinct stages of T cell development. We report that the neutralization of IL-7 early in fetal T cell development results in a decrease in the production of mature CD4 or CD8 ('single positive', SP) or CD4/8 negative ('double negative', DN) T cell phenotypes, as defined by their expression of CD3. This loss of T cell development was not complete, but it did include the development of gammadelta T cells. However, if IL-7 was neutralized at later stages of FTOC, the production of CD4/8 positive ('double positive', DP) T cells was increased, and if the addition of the antibody was delayed further, the production of mature SP T cells was increased. This last result could be extended to both alphabeta and gammadelta T cells. These data suggested that IL-7 played a negative regulatory role in the development of progressively mature T cells. Tissue sections of FTOC showed that IL-7 was expressed in the subcapsular region of the tissue where immature T cells reside. However, IL-7 was not detected in the medullary region where mature T cells are located. These data suggest that IL-7 not only supports the development of immature fetal T cells, but it may inhibit the development of mature T cells. The production of mature fetal T cells may, therefore, be delayed until their precursors enter the medullary microenvironment, where IL-7 production is low. In this way, T cells may be prevented from maturing until negative selection or anergy events eliminate or inactivate autoreactive clones.
DeLuca
Dominick
D
Department of Microbiology and Immunology, The University of Arizona, LSN 648, 1501 N Cambell Ave., Tucson, AZ 85724-5049, USA. deluca@u.arizona.edu
Clark
Dawn R
DR
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation; D002678:Chimera / Q000276:immunology; D005333:Fetus / Q000166:cytology / Q000276:immunology; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000276:immunology*; D007700:Kinetics; D008099:Liver / Q000166:cytology; D051379:Mice; D009500:Neutralization Tests; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
D000906:Antibodies; D015851:Interleukin-7