Tetraspanins in cellular immunity

Tetraspanins are a superfamily of integral membrane proteins involved in the organization of microdomains that consist of both cell membrane proteins and cytoplasmic signalling molecules. These microdomains are important in regulating molecular recognition at the cell surface and subsequent signal transduction processes central to the generation of an efficient immune response. Tetraspanins, both immune-cell-specific, such as CD37, and ubiquitously expressed, such as CD81, have been shown to be imp-ortant in both innate and adaptive cellular immunity. This is via their molecular interaction with important immune cell-surface molecules such as antigen-presenting MHC proteins, T-cell co-receptors CD4 and CD8, as well as cytoplasmic molecules such as Lck and PKC (protein kinase C). Moreover, the generation of tetraspanin-deficient mice has enabled the study of these proteins in immunity. A variety of tetraspanins have a role in the regulation of pattern recognition, antigen presentation and T-cell proliferation. Recent studies have also begun to elucidate roles for tetraspanins in macrophages, NK cells (natural killer cells) and granulocytes.     

Drosophila hemopoiesis and cellular immunity

In Drosophila melanogaster larvae, three classes of circulating cellular immune surveillance cells (hemocytes) can be identified: plasmatocytes, crystal cells, and lamellocytes. Plasmatocytes are professional phagocytes most similar to the mammalian monocyte/macrophage lineage and make up approximately 95% of circulating hemocytes. The other approximately 5% of circulating hemocytes consists of crystal cells, which secrete components necessary for the melanization of invading organisms, as well as for wound repair. A third cell type known as lamellocytes are rarely seen in healthy larvae and are involved in the encapsulation of invading pathogens. There are no obvious mammalian counterparts for crystal cells or lamellocytes, and there is no equivalent to the lymphoid lineage in insects. In this review, I will discuss what is currently known about Drosophila hemopoiesis and the cellular immune response and where possible compare it to vertebrate mechanisms.     

Lenalidomide enhances anti-myeloma cellular immunity

Lenalidomide is an effective therapeutic agent for multiple myeloma that exhibits immunomodulatory properties including the activation of T and NK cells. The use of lenalidomide to reverse tumor-mediated immune suppression and amplify myeloma-specific immunity is currently being explored. In the present study, we examined the effect of lenalidomide on T-cell activation and its ability to amplify responses to a dendritic cell-based myeloma vaccine. We demonstrate that exposure to lenalidomide in the context of T-cell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFN-γ, but not IL-10 expression. In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a decrease in T-cell expression of the inhibitory marker, PD-1. Lenalidomide also enhanced T-cell proliferative responses to allogeneic DCs. Most significantly, lenalidomide treatment potentiated responses to the dendritic cell/myeloma fusion vaccine, which were characterized by increased production of inflammatory cytokines and increased cytotoxic lymphocyte-mediated lysis of autologous myeloma targets. These findings indicate that lenalidomide enhances the immunologic milieu in patients with myeloma by promoting T-cell proliferation and suppressing inhibitory factors, and thereby augmenting responses to a myeloma-specific tumor vaccine.     

Importance of thymus-derived lymphocytes in cell-mediated immunity to infection

Peripheral blood lymphocytes from ten human neonates and ten adults were studied. Many more medium and large cells were identified in neonates, and the ultrastructure of the medium-sized lymphocytes resembled guinea pig transitional cells. There were 20 times more nucleoside-incorporating lymphocytes in the newborn samples, and a neonatal high-labeling cell was identified.     

Demonstration of anti-pancreatic cellular immunity in insulin-dependent diabetics

A significant inhibition of insulin response was found after incubation of islet cells with blood lymphocytes from 18 out 20 insulin-dependent diabetics. No inhibition was found in 22 control subjects.     

Impact of substance P on cellular immunity

Much evidence suggests a cross-talking between nerve fibers and the immunity system. The immunomodulation by substance P includes cell activation and proliferation of human cells, with cytokine and chemokine generation and release. Substance P was first isolated by Leeman et al. as an undecapeptide with important neurotransmitter-neuromodulator effects. In addition, substance P was shown to induce and mediate inflammation, angiogenesis, infections, intestinal mucosal immunity and stress. Substance P is able to activate several immune cells, such as CD4+ and CD8+ T lymphocytes, mast cells, NK cells and macrophages. In recent studies we have shown that substance P can activate interleukin-8, a CXC chemokine, demonstrating its involvement in immune cell chemoattraction. We believe that substance P is important in understanding the pathophysiology of inflammation.     

Studies on cellular immunity toSalmonella typhi in vitro

Salmonella typhi (strain Ty2—4446) cultivatedin vitro within the macrophage of mice immunised twice specifically with a high dose of killed vaccine, multiplied less intensively than in the cells of non-immunised control animals during 24 hours cultivation. In addition, a certain suppression of growth ofSalmonella enteritidis andSalmonella suis var. Kunzendorf was observed in the macrophages of mice immunised withSalmonella typhi vaccine. Double immunisation of mice with high doses of killed vaccine fromSalmonella enteritidis andSalmonella suis led to the mice macrophages being able to suppress multiplication of both homologous microbes andSalmonella typhi. The formation of such cross resistance in mice immunised with salmonella vaccines excludes the possible participation of O, H, and Vi antibodies in this phenomenon.