Interleukin-7 (IL-7) Knockout Mice. Implications for Lymphopoiesis and Organ-Specific Immunity

Abstract

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 genedeleted 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 αβ⁺ T-cells compared to γδ⁺ 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 αβ or γβ T-cells for IL-7. In general, IL-7 appears to serve as the major growth and differentiation factor for γβ T-cells. IL-7-/-mice are characterized by a block of maturation of Vγ3^low, CD24⁺ T-cells to Vγ3^high, CD24^low T-cells. Thus, IL-7 does not only represent a ‘maintenance factor’, but rather a cytokine required for sucessful thymic and extrathymic development and maturation of γδ T-cells. γδ⁺ intestinal intraepithelial lymphocytes (iIEL) are absent in IL-7-/-animals. In contrast, αβ⁺ iIEL can be detected in IL-7 gene-deleted animals, but not in γc, or in JAK-3 deficient mice suggesting that alternative cytokines may be involved in development of iIEL αβ⁺ T-cells, but not necessarily for γδ 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.

Key Words:

• Interleukin-7
• IL-7 knockout mice
• Intra-epithelial lymphocytes
• IEL
• γδ-T-cells
• αβ-T-cells
• T-cell growth factors
• Lymphopoiesis