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Professor
Department of Laboratory Medicine and Pathology
Cambridge, 1988, Ph.D.
612-625-1496 - office
612-625-1626 - lab
Lab website http://www.jamequist.umn.edu/
E-mail:james024@umn.edu
The Jameson lab is mainly focused on CD8 T cell responses against pathogens. Our studies involve defining optimally protective CD8 T cells, and the vaccination approaches that produce and sustain them. We also work on T cell trafficking, with special emphasis on the role of the transcription factor KLF2, which serves as a key regulator of T cell migration. Lastly, we investigate the mechanisms by which homeostatic mechanisms (rather than exposure to foreign antigens) can drive naïve CD8 T cells to acquire memory T cell characteristics, and the significance of such cells in host defense.
1) Protective immunity by CD8 T cells
CD8 T cells are capable of controlling many bacterial, viral and parasitic infections. Yet distinct vaccination approaches produce diverse populations of effector and memory CD8 T cells, raising questions about which populations are optimal at protective immunity (against a given pathogen), and how we can rapidly produce such cells by vaccination. We examine immunization methods that rapidly induce and sustain large numbers of CD8 T cells displaying features of memory or of “long-lived effector” cells, and evaluate their protective to control infections. These studies have led to the finding that, rather than classic memory phenotype cells, a population of long-lived effector cells show unexpectedly potent protection against certain bacterial and viral infections.
2) Function of KLF2 in control of T lymphocyte trafficking
Some years ago we discovered that the zinc-finger transcription factor KLF2 plays a key role in T cell migration, through regulation of numerous trafficking molecules involved in lymphoid tissue entry and egress. Interestingly, KLF2 expression is heterogeneous among memory T cells: KLF2 is highly expressed by memory CD8 T cells (both the classic “central” and “effector” memory populations) in lymphoid tissues and blood. However, KLF2 expression is extinguished in “Resident memory T cells” – populations found in the parenchyma of non-lymphoid tissues (as diverse as the small intestine, salivary gland and brain), which are critical for effective control of infections at barrier surfaces. Our studies suggest that induced downregulation of KLF2 targets (specifically the protein S1PR1, involved in T cell egress) is essential for establishment of resident memory cells.
3) Homeostatic mechanisms regulating naïve T cell responses
Memory T cells are not only produced during the response to foreign antigens: Our work has defined at least two distinct pathways in which naïve CD8 T cells acquire memory-like properties, through the response to cytokines (including IL-7, IL-15 and IL-4) and interaction with self peptide/MHC molecules. Such memory populations exist in normal unimmunized mice, and these cells show functional properties (including pathogen protection) similar to “true” memory cells. We are investigating the role of these population in normal immunity, and ways to harness “homeostatic memory” cells for improved protection against infection. Since lymphopenia can induce generation of homeostatic memory cells, these findings have relevance for immune function in immunocompromized individuals.
Furthermore, we have found that heterogeneity among naïve CD8 T cells dictates both how they will respond to homeostatic cues, and how they will respond to foreign antigen stimulation. We are investigating the basis by which some naïve CD8 T cells are much more potent than others in their response to infection, and determining how this influences immune competence.