[Show abstract][Hide abstract] ABSTRACT: CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of) mouse CD1d on the surface of cells. Low pH (3.0) acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.
PLoS ONE 08/2013; 8(8):e72867. DOI:10.1371/journal.pone.0072867 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Influenza A viruses are enveloped viruses belonging to the family Orthomyxoviridae that encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized.
Animal Health Research Reviews 06/2010; 11(1):53-72. DOI:10.1017/S1466252310000137
[Show abstract][Hide abstract] ABSTRACT: Histamine (HA) is one of the most versatile biogenic amines with multiple physiological functions in the central nervous system (CNS), the respiratory and the intestinal tract due to its ability to induce severe inflammatory reactions. More recently, a number of studies have established that besides its most obvious contribution in allergic reactions, HA also exerts more subtle regulatory functions influencing the orientation of the immune response, thus rekindling interest in this field of investigation. It can influence numerous functions of the cells involved in the regulation of immune responses and hematopoiesis of macrophages, dendritic cells, T lymphocytes, B lymphocytes and endothelial cells. All these cells express histamine receptors and also secrete histamine, which can selectively recruit major effector cells into tissue sites and affect their maturation, activation, polarization, and effector functions leading to chronic inflammation. Histamine regulates antigen-specific T-helper 1 (Th1) and T-helper 2 (Th2) cells, as well as related isotype specific antibody responses. Histamine acts through its receptor called as histamine receptor (H1-H4) subtypes, which positively interferes with the peripheral antigen tolerance induced by T-regulatory cells (Tregs) through several pathways. Natural killer T (NKT) cells are the heterogeneous population of innate immune T cells that have been attracted the attention of many researchers due to their potential to regulate immune responses to a variety of pathogens, tumors, autoimmune diseases etc. A majority of NKT cells in mice are invariant NKT (iNKT) cells and are considered to be immunoregulatory in nature, due to their ability to promptly produce both Th1 and Th2 cytokines rapidly upon activation. In this chapter, we have tried to focus on HA participation in NKT cell activation by functional tuning to ensure optimal cytokine production, which leads to the recruitment and activation of other immune cells involved in inflammatory responses mediated through eosinophils, mast cells, neutrophils, conventional T lymphocytes, dendritic cells etc.
Biomedical Aspects of Histamine, 01/2010: pages 103-132; , ISBN: 978-90-481-9348-6
[Show abstract][Hide abstract] ABSTRACT: Natural killer T (NKT) cells are a T cell subpopulation known to possess immunoregulatory functions and recognize CD1d molecules. The majority of NKT cells express an invariant TCR [alpha] chain rearrangement and are called Type I NKT cells; all other NKT cells are Type II. In the current study, we have analyzed the roles for NKT cell subsets in the host’s innate antitumor response against the murine NS0 B-cell lymphoma model in vivo. As the NS0 cell line lacks detectable cell surface CD1d expression, murine CD1d1 cDNA or empty vector was transfected into NS0 cells to generate CD1d+ and control cell lines. In tumor-bearing mice, we found that Type I NKT cells conferred protection in a CD1d-dependent manner, whereas Type II NKT cells exhibited inhibitory activity. Pro- and anti-inflammatory cytokines secreted by splenocytes from tumor-bearing mice were predictive of tumor progression. Myeloid suppressor cells (CD11b+Gr1+) were present in larger numbers at the tumor site and in the spleen of tumor-bearing Type I NKT-deficient mice, suggesting a possible inhibition of antitumor immunosurveillance mediated by these cells. Therefore, there are distinct roles for NKT cell subsets in response to a B-cell lymphoma in vivo, pointing to potential novel targets to be exploited in the immunotherapy of blood cancers.