IL-2, a cytokine produced by T cells, is a key regulator of immune responses and T cell homeostasis. Controlling the availability of IL-2 is consequently of significant import to the immune system. Like other cytokines, IL-2 is thought to function as a soluble agonist, transiently present when secreted in response to appropriate stimuli. In this study, we show that the most salient properties of IL-2, propagation and control of T cell responses, are mediated in vivo by bound and not free cytokine and specifically by heparan sulfate-bound IL-2. These findings necessitate a new look at how IL-2 regulates immune responses and support the notion that the microenvironment plays a determining role in modulating the character of immune responses.

The role of interleukin-2 (IL-2) in thymic development is uncertain. Not surprisingly, IL-2 knockout (KO) mice have been used to address this question. However, as we report here, such mice are chimeric, containing both IL-2 KO cells and IL-2-expressing cells transferred in utero from their heterozygous mothers. These cells produce IL-2 in amounts detectable by conventional means, and their presence in lymphoid tissues confounds efforts to define the true IL-2 KO phenotype. To minimize the amount of IL-2 available to the thymus, we subjected recombinase activating gene-1 KO mice to bone marrow transplantation using IL-2 KO donors, and then followed the reconstitution of the thymus. The thymuses of these mice became increasingly aberrant over time, including abnormalities in both stromal cells and thymocytes. These results demonstrate that IL-2 is critical to several aspects of thymic function, a finding previously obscured by the presence of IL-2 in IL-2 KO mice.

The production of auto-antibodies is one of the predominant characteristics of autoimmune disorders. Because IL-2 deficient mice develop autoimmunity, we asked how IL-2 deficiency might impair endogenous mechanisms of B cell tolerance. To this end, we mated BALB/c anti-dsDNA H chain knock-in mice, in which B cells producing anti-dsDNA antibodies are properly regulated, with IL-2 deficient mice and assessed the phenotype of their offspring. IL-2 deficient mice expressing the antidsDNA H chain knock-in allele developed anti-dsDNA antibodies of both IgM and IgG isotypes. Production of these antibodies occurred through the disruption of several mechanisms of endogenous tolerance, including deletion, maturational arrest, and follicular exclusion. In summary, our results suggest that IL-2 plays an important role in regulating B cell tolerance.

Although research has demonstrated bovine viral diarrhea virus (BVDV) can be transmitted by a fomite, there are no published studies on the longitudinal survival of BVDV on common materials and within liquids used in livestock production that could serve as fomites. The objective of this study was to evaluate the longitudinal survival of a type lb, non-cytopathic (NCP) BVDV on fomites in the presence or absence of a novel, synthetic mucus.

Fomites have been shown to play a role in the transmission of bovine viral diarrhea virus (BVDV). However, there are no published reports on the length of time BVDV can survive on fomites. In the current study, we applied a type 1b, non-cytopathic (NCP) BVDV isolate to clothing, materials common to livestock production settings, and various feedstuffs. Additionally, we created a synthetic mucus phosphate buffered saline (PBS) solution and added BVDV to determine whether mucus impacted BVDV survival. Overall, the ability to recover BVDV after application to potential fomites decreased as the length of incubation increased. The BVDV strain tested in this study exhibited longer survival times in two aqueous solutions (water and PBS), two non-porous materials (latex and enameled metal), and one porous material (paper) than in other potential fomites. One non-porous material (galvanized metal) and two porous materials (soil and pine) tended to have a lower chance of BVDV recovery. No virus was recovered from denim, cotton t-shirt, mineral and salt blocks. For the total mixed ration, BVDV was recovered in one replicate, for up to eight hours post-application; however, all other replicates were negative. The molasses-urea lick in all three replicates was contaminated, therefore they were not tested. Based on these findings, a type 1b, NCP BVDV was capable of surviving after application to various materials used in livestock production. In the presence of mucus, BVDV was protected from degradation for longer periods of time.