Developmental and Anatomical Patterns Of IL-2 Gene Expression in Vivo in The Murine Thymus

Interleukin-2 (IL-2) is a potent growth factor that mature T lymphocytes synthesize and use as a proliferation signal. Much controversy has arisen concerning whether it is used to drive the extensive proliferation of immature pre-T cells in the thymus. Immature thymocytes acquire the competence to express IL-2 at an early stage, but it has remained uncertain whether they are activated to exercise this competence in vivo. Therefore, we have used in situ hybridization and immunohistochemistry on serial sections obtained from fetal and adult thymuses of normal C57BL/6 mice and of mice bearing the scid defect to determine where, when, and whether IL-2 is expressed in vivo. Our results show a striking spatial and temporal pattern of IL-2 expression in the normal fetal thymus. We detected a burst of IL-2 mRNA accumulation at day 14.5 of gestation, which rapidly decreased by day 15. At day 15, we observed maximal IL-2 protein production that subsequently decreased by day 16 of gestation. Both in situ hybridization and immunohistochemical staining revealed an unexpectedly strict localization of IL-2 expressing cells to patches around the periphery of the fetal thymus, creating a previously unrecognized compartment of high IL-2 protein content. IL-2 production in the day-15 fetal thymus appeared to be unaffected by the scid mutation, indicating that this response is likely to be T-cell receptor (TcR)-independent. Several features distinguish the IL-2 induction pattern in the adult thymus from that in the fetal thymus. In the normal adult thymus, IL-2-expressing cells are extremely rare (found at a frequency of 10^(-7)), but they are reproducibly detectable as isolated cells in the outer cortex and subcapsular region of the thymus. Unlike the fetal thymic IL-2 producers, the IL-2 producers in the adult thymus are completely eliminated in mice homozygous for the scid mutation. This suggests that the IL-2-expressing cells in the normal adult thymus are of a more mature phenotype than the immature, TcR-negative cells that accumulate in the scid adult thymus. Thus, our work demonstrates that two developmentally distinct types of cell interactions induce IL-2 expression in vivo: one, a broadly localized interaction in day 14-15 fetal thymus that is unaffected by the scid mutation; the other, a rare event that occurs asynchronously from late fetal through adult life, but which is completely eliminated by the scid defect. These results imply that significant differences exist between the physiological processing of thymocytes in the fetal and postnatal thymic microenvironments

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

Concepts for on-board satellite image registration. Volume 3: Impact of VLSI/VHSIC on satellite on-board signal processing

Anticipated major advances in integrated circuit technology in the near future are described as well as their impact on satellite onboard signal processing systems. Dramatic improvements in chip density, speed, power consumption, and system reliability are expected from very large scale integration. Improvements are expected from very large scale integration enable more intelligence to be placed on remote sensing platforms in space, meeting the goals of NASA's information adaptive system concept, a major component of the NASA End-to-End Data System program. A forecast of VLSI technological advances is presented, including a description of the Defense Department's very high speed integrated circuit program, a seven-year research and development effort

The study of human venous system dynamics using hybrid computer modeling

A computer-based model of the cardiovascular system was created emphasizing effects on the systemic venous system. Certain physiological aspects were emphasized: effects of heart rate, tilting, changes in respiration, and leg muscular contractions. The results from the model showed close correlation with findings previously reported in the literature

Modal strain energies in COSMIC NASTRAN

A computer program was developed to take a NASTRAN output file from a normal modes analysis and calculate the modal strain energies of selected elements. The FORTRAN program can determine the modal strain energies for CROD, CBAR, CELAS, CTRMEM, CQDMEM2, and CSHEAR elements. Modal strain energies are useful in estimating damping in structures

Computer simulation studies of the venous circulation

Analog simulation of human cardiovascular system with emphasis on venous circulatio

Coal feed component testing for CDIF

Investigations conducted during the conceptual design of the Montana MHD Component Development and Integration Facility (CDIF) identified commercially available processing and feeding equipment potentially suitable for use in a reference design. Tests on sub-scale units of this equipment indicated that they would perform as intended

The Law of Contract and the Concept of Change: Public and Private Attempts to Regulate Modification, Waiver, and Estoppel

This article argues that contractual change is inherently problematic because contract and change are fundamentally antithetical. Because change is inevitable, however, the law of contract attempts to regulate the effect of change. These attempts are divided into two realms: public regulation, including the preexisting duty rule and its substitutes, and private regulation, including contractual no oral modification and no oral waiver clauses. The article criticizes not only the preexisting duty rule but also the duress and good faith tests that have been suggested as substitutes. Instead, the article proposes a coercion test, which is stated in detail and which is compared with duress in a matrix of cases. On the private side, the article would validate clauses that require modifications and waivers to be written, although a limited exception for estoppel (which is distinguished from waiver and modification) is recognized. The article rejects calls for complete validation or invalidation of such clauses. The paper recognizes the benefits of those clauses, especially with respect to course of performance and its effects under the Uniform Commercial Code. After examining several decades of case law, however, the article concludes that courts cannot realistically be expected to uphold such clauses in the face of reasonable, material reliance. When a party seeks public (i.e., judicial) enforcement of a private regulation, public concerns must enter any decision to enforce that regulation. While the legislation proposed in this article would generally uphold these private regulations, circumstances are suggested in which such contractual clauses will fail. Provisions to replace UCC sections 1-205, 2-208, and 2-209 are included

Orbital-free Bond Breaking via Machine Learning

Machine learning is used to approximate the kinetic energy of one dimensional diatomics as a functional of the electron density. The functional can accurately dissociate a diatomic, and can be systematically improved with training. Highly accurate self-consistent densities and molecular forces are found, indicating the possibility for ab-initio molecular dynamics simulations