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Although integrin receptors have been shown to function as costimulatory molecules on mature thymocytes and T cells, it is not known whether these receptors can function as costimulatory molecules on immature thymocytes. Previous studies have shown that the expression of alpha4 and alpha5 integrins were significantly higher on immature, adult CD4(-)CD8(-) thymocytes than on either mature thymocytes or T cells, suggesting that these receptors are involved in early thymocyte development. In this study, we show that day 16 fetal thymocytes express levels of alpha4 and alpha5 equivalent to those of adult CD4(-)CD8(-) thymocytes. Immobilized fibronectin, a ligand for alpha4 and alpha5 integrins, was found to enhance the CD3-dependent proliferation of these fetal thymocytes. In the presence of IL-7, the magnitude of the proliferative response increased with time of incubation, resulting in a dramatic increase in the percentage of gammadelta thymocytes. The enhancement of proliferation by fibronectin was abrogated by soluble antibodies against alpha4 and alpha5, whereas immobilized mAb to alpha4 and alpha5 substituted for fibronectin in enhancing CD3-dependent proliferation, demonstrating that alpha4 and alpha5 integrins were responsible for the enhanced proliferation by fibronectin. Anti-alpha4 mAb enhanced proliferation of fetal thymocytes by 100%, whereas anti-alpha5 mAb and anti-CD28 mAb enhanced proliferation by 25%. Other costimulatory molecules, such as CD2, FcRgamma, and Thy-1, had no effect on the CD3-dependent proliferation of day 16 fetal thymocytes. This study demonstrates that alpha4 and alpha5 integrins are capable of costimulating fetal thymocytes., (Copyright 1998 Academic Press.)

The development of IL-4-producing effector T cells during a type 2 immune response requires signaling through B7 ligands, but probably not CD40 ligands. Here, William Gause and colleagues review the still controversial role of CD28 and CTLA-4 on T cells, and B7-1 and B7-2 on antigen-presenting cells, and provide a model to incorporate recent findings.

Integrins are a family of cell surface receptors which mediate the adhesion of cells to each other or to extracellular matrix (ECM) proteins. The interaction of integrins with their ligands or counter-receptors was initially considered to be a one-way process in that cells actively regulate the interaction of integrins with their ligands ('inside-out signal'). In contrast, it was not obvious that cells would receive a signal from the outside via the integrin heterodimers following ligand binding ('outside-in signal'). Recent evidence increasingly supports the active role of integrins in cell activation and proliferation. Many reports describe the effects of integrin-mediated signaling in lymphoid cells. Our studies of gamma/delta T cells, expressing the beta 3 integrin vitronectin receptor (VNR), reflect some of the consequences this active interaction between lymphocytes and the ECM could have for T cell activation and differentiation. The VNR has been described as a T cell costimulatory molecule. We recently reported that the VNR has the potential to stimulate cytokine secretion in T cell hybridomas without involvement of T cell receptor-mediated signals. Further studies demonstrated tyrosine phosphorylation of proteins following VNR cross-linking and the interaction of the VNR with protein kinases. Intensive research focuses on the signal transduction mechanisms of integrins and their interaction with other costimulatory or activation molecules. This knowledge is important to better understand the role of adhesion molecules, the ECM, and the cellular microenvironment for lymphocyte activation and differentiation.

Fungistasis which occurs in soil has also been reported to exist in seawater. Nannochloris sp. (Chlorophyta) found along the west coast of Florida, has been shown to elaborate a compound which is cytolytic towards Ptychodiscus brevis, the Florida red tide organism. Aponin, a chloroform extract containing the cytolytic compound or compounds, was tested on the spore germination of two fungi, Dendryphiella salina, a facultative marine organism and Curvularia sp. a terrestrial one. Aponin was stimulatory towards D. salina at all concentrations tested, while Curvularia sp. was stimulated at the highest concentration used but inhibited at the lower concentrations. The culture age of the two fungi did not alter the relative sensitivity of both fungi towards aponin but the germination percentage of Curvularia sp. was affected by the culture age. An aqueous extract of Nannochloris sp. was also tested on the two fungi and was shown to be inhibitory to both. The results seem to indicate that more than one compound from Nannochloris sp. is capable of affecting spore germination indicating that this alga might be playing a role in the reported fungistasis in seawater. Gulf seawater was tested and found to have little if any fungistatic activity.