Spontaneous Expression of Interleukin-2 In Vivo in Specific Tissues of Young Mice

Journal of Immunology Research, Aug 2018

In situ hybridization and immunohistochemistry were used to determine the spectrum of tissues in which interleukin-2 (IL-2) mRNA and protein are found in healthy, normal young mice. In neonatal animals, IL-2 is expressed specifically by distinct, isolated cells at three major sites: the thymus, skin, and gut. Based on morphology and distribution, the IL-2-expressing cells resemble CD3ε

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://downloads.hindawi.com/journals/jir/1998/012421.pdf

Spontaneous Expression of Interleukin-2 In Vivo in Specific Tissues of Young Mice

Spontaneous Expression of Interleukin-2 In Vivo in Specific Tissues of Young Mice JULIA A.YANG-SNYDER 0 ELLEN V.ROTHENBERG 0 0 aHoward Hughes Medical Institute and Department of Pharmacology K516, University of Washington , Box 357750, Seattle, Washington 98195-7750 , USA In situ hybridization and immunohistochemistry were used to determine the spectrum of tissues in which interleukin-2 (IL-2) mRNA and protein are found in healthy, normal young mice. In neonatal animals, IL-2 is expressed specifically by distinct, isolated cells at three major sites: the thymus, skin, and gut. Based on morphology and distribution, the IL-2-expressing cells resemble CD3e T cells that are also present in all these locations. Within the thymus of postweanling animals, both TcRafl and TcR),6 lineage cells secrete "haloes" of the cytokine that diffuse over many cell diameters. Within the skin, isolated cells expressing IL-2 are seen at birth in the mesenchyme, and large numbers of IL-2-expressing cells are localized around hair follicles in the epidermis in 3-week-old animals. At this age, a substantial subset of CD3 cells is similarly localized in the skin. Significantly, by 5 weeks of age and later when the CD3e cells are evenly distributed throughout the epidermis, IL-2 RNA and protein expression are no longer detectable. Finally, within the intestine, IL-2 protein is first detected in association with a few discrete, isolated cells at day 16 of gestation and the number of IL-2 reactive cells increases in frequency through El9 and remains abundant in adult life. In postnatal animals, the frequency of IL2-positive cells in villi exceeds by greater than fivefold that found in mesenteric lymph node or Peyer's patches. Overall, these temporal and spatial patterns of expression provide insight into the regulation of IL-2 in vivo and suggest a role for IL-2 expression distinct from immunological responses to antigen. Dendritic epidermal T cells; gut-associated lymphocytes; TCR-yt3 thymocytes; TCR-a/3 thymocytes; in situ hybridization; immunohistochemistry; developmental regulation; interleukin-2 INTRODUCTION Interleukin-2 (IL-2) has been best studied as a growth factor secreted by activated T cells in the course of the immune respohse. Its expression is strictly dependent on inducing stimuli, with requirements forseparate signals from Ca+2-dependent, ras-dependent, and 1995; Serfling et al., 1995). These requirements are met in mature T cells when they encounter antigen on antigen-presenting cells, thereby delivering coordinated signals triggered by the crosslinking of TcR/ CD3 complexes, CD4 (or CD8 in some cases), and CD28. Accordingly, analysis of the cis and trans regulatory elements critical for IL-2 expression has shown several discrete protein-DNA interactions that require activation by TcR/CD3- and/or CD28dependent signaling mediators (Jain et al., 1995; Serfling et al., 1995) . The observation that IL-2 is also expressed primarily or exclusively by T cells has led to a general assumption that the primary function of IL-2 expression in vivo is to regulate T-cell clonal expansion as triggered by T-cell recognition of foreign antigen. This assumption has been challenged in recent years by the phenotype of IL-2 "knockout" mice. Animals homozygous for targeted disruption of the IL-2 gene show initially normal numbers of T cells of various subsets and detectable but relatively subtle defects in their immediate proliferative responses to antigen (Schorle et al., 1991; Ktindig et al., 1993; Krimer et al., 1994; Cousens et al., 1995; Kneitz et al., 1995) . By contrast, multiple aspects of their longterm hematopoietic regulation and lymphocyte homeostasis are disrupted (Sadlack et al., 1993, 1995; Krimer et al., 1995; Reya, 1996) . These findings raise several questions about the role of IL-2 expression in vivo. First, is IL-2 expressed in homeostatic contexts as well as in acute immune responses? Second, does IL-2 expression regulate hematopoietic populations in nonlymphoid tissues? Lastly, is mature cell behavior affected by prior exposure or lack of exposure to IL-2 during development? In order to address these questions, we systematically examined various organs of normal young mice to determine where IL-2 is detectably expressed. Our studies show that IL-2 mRNA and protein are associated with specific tissues in situ. These tissues invariably contain T cells, suggesting that IL-2 may be involved in regulating lymphocytic and/or hematopoietic function(s) at these sites. RESULTS Overall Distribution of IL-2-Expressing Cells in Neonatal Mice To survey the range of tissues that might express the IL-2 gene in mice, neonatal mouse body sections were analyzed by in situ hybridization with 35S-labeled probes. The results of these analyses showed that most tissues of the body were devoid of hybridization above background, as established with sense-strand control probes. Brain, heart, lung, liver, stomach, bladder, and oth (...truncated)


This is a preview of a remote PDF: http://downloads.hindawi.com/journals/jir/1998/012421.pdf

Julia A. Yang-Snyder, Ellen V. Rothenberg. Spontaneous Expression of Interleukin-2 In Vivo in Specific Tissues of Young Mice, Journal of Immunology Research, 5, DOI: 10.1155/1998/12421