Interleukin-7 (IL-7) knockout mice. Implications for lymphopoiesis and organ-specific immunity.
Interleukin-7 (IL-7) is produced by both immune and non-immune cells including stromal cell lines, B-cells, monocytes/macrophages, follicular dendritic cells, keratinocytes, and gut epithelial cells. The development of IL-7 knockout mice aided to elucidate the role of this multifaceted cytokine in lymphopoiesis. Additionally, IL-7 gene-deleted mice may represent an excellent model in order to define the functional role of locally secreted IL-7 in organ-specific immunity and in anti-microbial responses as well. For instance, analysis of IL-7 gene-deleted mice revealed reduced numbers of total T-lymphocytes with preservation of the CD4/CD8 ratio and increased ratio of alpha beta + T-cells compared to gamma delta + T-cells. Transition of pro-T-cells to pre-T-cells was impaired. Cell marker analysis of thymocytes in IL-7 -/- mice suggested that IL-7 may induce expression of as yet unidentified cytokine receptors, and that IL-7 may also be critically involved in T-cell differentiation. However, there are clear differences in the requirements of alpha beta or gamma delta T-cells for IL-7. In general, IL-7 appears to serve as the major growth and differentiation factor for gamma delta T-cells. IL-7 -/- mice are characterized by a block of maturation of V gamma 3low, CD24+ T-cells to V gamma 3high, CD24low T-cells. Thus, IL-7 does not only represent a 'maintenance factor', but rather a cytokine required for successful thymic and extrathymic development and maturation of gamma delta T-cells. gamma delta + intestinal intraepithelial lymphocytes (iIEL) are absent in IL-7 -/- animals. In contrast, alpha beta + iIEL can be detected in IL-7 gene-deleted animals, but not in gamma c, or in JAK-3 deficient mice suggesting that alternative cytokines may be involved in development of iIEL alpha beta + T-cells, but not necessarily for gamma delta T-cells. To this end, IL-7 has predominantly been studied in the context of B- and T-cell development. With the availability of IL-7 gene-deleted mice, the paracrine effects of IL-7, which may be secreted in vivo by non-immune cells including keratinocytes or gut epithelial cells, can now be critically examined.
Maeurer
M J
MJ
Department of Medical Microbiology, University of Mainz, FRG. maeurer@omalley.zdv.uni-mainz.de
Lotze
M T
MT
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology*; D019891:Leukopoiesis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D015851:Interleukin-7