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Kamal Khanna, Ph.D. |
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An effective immune response depends on the large-scale, but carefully regulated, movement of cells within and between lymphoid and peripheral tissues. Secondary lymphoid organ structure is the underlying regulator of immune responses and is responsible for promoting interactions between cells as well as between cells and extracellular matrix. In recent years, our understanding of events in secondary lymphoid tissues has been advanced by the use of multiphoton microscopy to visualize lymphocyte movement. Nevertheless, much remains to be revealed about the microanatomy of antigen-specific primary and memory CD8 T cell responses, with relatively limited data currently available from in situ visualization of endogenous CD8 T cell responses. My recent results have helped illuminate the landscape under which the endogenous CD8 T cell immune response occurs (Khanna, et.al. Science, 2007). These findings have set the stage for in situ identification of the cell types and other factors that control the processes driving each anatomical phase of the immune response to infection. In my lab we will combine well established research methods with the novel tools that I have recently developed, which include: (i) whole mount confocal microscopy techniques using in situ MHC class I tetramer staining to allow visualization of endogenous antigen-specific CD8 T cells in virtually any tissue. This powerful method increases detection sensitivity and preserves the functional/physical anatomy of organs being studied. (ii) A new transgenic mouse (CD11c-mCherry) that expresses a red fluorescent protein (RFP) variant called mCherry under control of the CD11c promoter to allow visualization of dendritic cells (DC) in vivo and (iii) multi-photon imaging in vivo imaging. Investigate the role of sphingosine-1-phosphate (S1P) receptors in the local migration and localization of CD8 T cells and DC after infection: S1P receptors play a role in migration and retention of T cells in primary and secondary lymphoid organs. In collaboration with Tim Hla’s lab we will use novel mouse models to determine the role of S1P receptors in T cell and DC homing and migration under normal conditions as well as during infection. We will also employ dynamic intravital two photon microscopy to visualize the role of S1P receptors in T cell and DC activation and migration after infection. Visualize the dynamics of CD8 T cell immune response during latent herpesvirus infections: Herpesvirus infections are considerably widespread, where the virus establishes a life long infection in its host even in the presence of concomitant immunity. Understanding the co-existence of latent virus in the presence of an active immune system is an important biological problem that offers a fascinating model for studying T cell immunobiology. Following MCMV infection certain immunodominant epitope (during lytic phase of MCMV infection) specific CD8 T cells contract and continue to “deflate” during the latent phase of the infection. However, other epitope specific CD8 T cells continue to gradually expand throughout the life of the host long after latency is established. The mechanisms that contribute to this intriguing interplay of “deflationary” vs. “inflationary” anti-viral CD8 T cell responses are poorly understood. Thus, one of my goals will focus on understanding the dynamics of the immune system during latent herpesvirus infections. |
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| Two Photon confocal microscopy: Many elegant studies recently have pioneered the use of two photon microscopy to visualize T cell activation and migration in an intact mouse or in tissue explants. My lab is equipped with a state of the art two photon imaging system to perform intravital dynamic imaging of immune cells in vivo. My lab uses novel mice models to visualize the role of various proteins including S1P1R in T cell and dendritic cell activation and migration. In addition, my lab will focus on imaging the onset of a primary as well as a secondary immune response to viral and bacterial infection. To this end, fluorescent viruses and bacteria will be used to visualize the interplay between the antigen presenting cells and the responding antigen specific T cells in live animals and in explanted secondary lymphoid organs. Therefore the overall goal of my lab is to identify the factors and the role they play in controlling the anatomy of a primary and secondary immune response. In doing so, we hope to explicate the underlying mechanisms that guide the complex movement of T cells during infection and recall responses in lymphoid and non-lymphoid tissues. These studies will help us understanding how a productive immune response takes place in vivo, and this information will provide clues to improving vaccine design.Selected Publications: | ||||||
| To search Pubmed for publications by Dr. Khanna, please click here.
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