[85-88] Other analogues of αGalCer that are able to skew conventional CD4+ T-cell responses more towards either a Th1- or a Th2-like profile will be introduced into clinical studies. In the near selleck kinase inhibitor future, it may be possible to differentially activate or inhibit type I and type II NKT cells for the development of novel immunotherapeutic protocols in the treatment
and prevention of autoimmune diseases. Mechanisms by which NKT cell subsets modulate immunity generally follow events and their interactions with other immune cells after activation by their respective lipid antigens, e.g. αGalCer and sulphatide for type I and type II NKT cell subsets, respectively. As DCs play a crucial role not only in the activation of NKT cells but also may be central to their role in the regulation of immune responses, we will first consider NKT–DC interactions and their control of NKT cell-mediated modulation of
autoimmune disease. The advent of intravital imaging now enables the cell dynamics and function of T-cell–DC interactions to be investigated in vivo. Considerable new information provided by the application of 2P microscopy has been reported about the cellular and molecular dynamics of conventional CD4+ and CD8+ T-cell–DC interactions in vivo.[51, 54] While NKT–DC interactions are also central to the regulation of many immune responses MAPK inhibitor and diseases, less is currently known Carnitine palmitoyltransferase II about the dynamics of movement, recirculation and interaction between NKT cells and DCs in vivo.[51, 54] Some recent observations made using in vivo imaging of NKT–DC interactions are presented in Table 6. A key finding is that bidirectional NKT
cell–DC interactions can elicit and amplify innate and adaptive immune responses. Hence, intravital imaging has identified a central role for NKT cells in the context of other immune cells during various immune responses.[51, 54] This further underscores the importance of learning more about different NKT cell subsets and developing more experimental approaches to track these NKT cell subsets by in vivo imaging. In such studies, it is essential to monitor before and after antigen stimulation: (i) the tracking patterns of type I and type II NKT cells from blood into peripheral tissues (e.g. lymph nodes, spleen, liver), (ii) the differences in the number, time and stability of encounters of these NKT subsets with DCs, (iii) the time and sites of migration of these subsets after DC interaction, and (iv) these various parameters in environments of health (e.g. normal disease-free mouse strains) or disease (e.g. mouse strains that develop different autoimmune diseases, as described below).