David Masopust, Ph.D.
T cell migration, differentiation, and memory development in response to infections
My laboratory studies CD8 and CD4 T cell responses to a variety of viral and bacterial infections to help understand the development of immunological protection from re-infection. We observe and manipulate pathogen specific T cell responses over time by using MHC tetramers, adoptive transfer of transgenic T cells, fluorescence flow cytometry and sorting, and gene microarry analysis. Upon activation in lymphoid tissue, rare pathogen-specific naïve T cells proliferate, acquire effector functions, disseminate throughout the organism, and contribute to the eradication of pathogens. In situations where antigen is successfully eliminated, most effector T cells die by apoptosis. However, a fraction of effector T cells escape death and differentiate into long-lived memory T cells that contribute to protective immunity. We are currently dedicated to elucidating the developmental cues that govern T cell migration to different anatomical locations, commitment to the memory lineage, and the contribution of memory T cell differentiation state and location to protection from re-infection. Memory T cells that reside at common portals of pathogen entry or infection, especially the intestinal mucosa, are of particular interest. By understanding these issues, we hope to contribute to the development of better vaccination strategies, and are currently focused on informing development of a protective HIV vaccine.
Selected Recent Publications:
- Steinert EM, Schenkel JM, Fraser KA, Beura LK, Manlove LS, Igyarto BZ, Southern P, Masopust D. 2015. Quantifying memory CD8 T cells reveals regionalization of immunosurveillance. Cell. 161:737-49.
- Beura LK, Anderson KG, Schenkel JM, Locquiao JJ, Fraser KA, Vezys V, Pepper M, Masopust D. 2015. Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. J Leuk Bio, 97:217-25.
- Schenkel JM, Masopust D. 2014. Tissue-resident memory CD8 T cells. Immunity. 41:886-897.
- Schenkel JM, Fraser KA, Beura LK, Vezys V, Masopust D. 2014. Resident memory CD8 T cells trigger a rapid organ defense response through cytokines. Science. 346:98-101.
- Beura LK, Masopust D. Snapshot: Tissue Resident Memory T cells. 2014. Cell.
- Schenkel JS, Fraser KF, Masopust D. 2014. Cutting Edge: Resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs. J Immunol. 192:2961-4.
- Anderson KG, Mayer-Barber K, Sung H, Beura L, James BR, Taylor JJ, Qunaj L, Griffith TS, Vezys V, Barber DL, Masopust D. 2014. Discrimination of vascular and tissue leukocytes.Nature Protocols 9:209-22.
- Fraser KA, Schenkel JM, Jameson SC, Vezys V, Masopust D. 2013. Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. Immunity. 39:171-83.
- Masopust D, Schenkel JM. 2013. The integration of T cell migration, differentiation and function. Nature Reviews Immunology. 13:309-20.
- Schenkel, JM, Fraser KA, Vezys V, Masopust D. 2013. Sensing and alarm function of resident memory CD8+ T cells. Nature Immunology. 14:509-13.
- Anderson KG, Sung H, Skon CN, Lefrancois L, Deisinger A, Vezys V, Masopust D. 2012. Cutting Edge: Intravascular staining redefines lung CD8 T cell responses. J Immunol. 189:2702-6.
- Casey KA, Fraser KA, Schenkel JM, Moran A, Abt MC, Beura LK, Lucas PJ, Artis D, Wherry EJ, Hogquist K, Vezys V, Masopust D. 2012. Antigen independent differentiation and maintenance of effector-like resident memory T cells in tissues. 2012. J Immunol. 188:4866-75.
- Masopust D, Picker EJ. 2012. Hidden memories: frontline memory T cells and early pathogen interception. J Immunol. 188:5811-7.
- Masopust D, Choo D, Vezys V, Wherry EJ, Duraiswamy J, Akondy RS, Wang J, Casey KA, Barber DL, Fraser KA, Kawamura KS, Webby RJ, Brinkmann V, Butcher EC, Newell KA, Ahmed R. 2010. Dynamic T cell migration program establishes resident memory within intestinal epithelium. J Exp Med, 207:553-64.
- Jameson SC, Masopust D. 2009. Diversity in T-cell memory: An embarrassment of riches. Immunity. 31:859-71.
- Vezys V, Yates A, Casey KA, Lanier G, Ahmed R, Antia R, Masopust D. 2009. Memory CD8 T cell compartment grows with immunological experience. Nature457:196-9.