Renukaradhya Gourapura

Forming a complex with MHC class I molecules interferes with mouse CD1d functional expression.

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.

The Role of Histamine in Immunoregulation in Context of T-Regulatory and Invariant NKT Cells

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.