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

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 (+) T cells that are also present in all these locations. Within the thymus of postweanling animals, both TcRαβ and TcRγδ 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 CD3ε (+) cells is similarly localized in the skin. Significantly, by 5 weeks of age and later when the CD3ε (+) 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 IL- 2-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.