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Research Interests:
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.
Selected Recent Publications:
- Masopust, D, Vezys V, Ahmed R. A brief History of CD8 T cells. In press,Eur J Immunol.
- Constantin CM, Masopust D, Gourley TS, Grayson J, Strickland OL, Ahmed R, Bonney EA. 2007. Normal virus-specific CD8 T cell responses during pregnancy with persistent viral infection of placenta. J Immunol.179:4383-9.
- Radziewicz H, Ibegbu CC, Workowski KA, Obideen K, Wehbi M, Hanson HL, Masopust D, Wherry EJ, Altman JD, Rouse BT, Freeman GJ, Ahmed R, Grakoui A. 2007. Liver infiltrating lymphocytes in chronic human HCV infection display an exhausted phenotype with high PD-1 expression and low CD127 expression. J Virol. 81:2545-53.
- Masopust D, Krishna KM, Ahmed R. 2007. Quantitating the magnitude of the LCMV-specific CD8 T cell response: it’s even bigger than we thought. J Virol. 81:2002-11.
- Vezys V, Masopust D, Kemball C, Barber DL, Loomis J, Barber GN, Ahmed R, Pearson TC, Larsen CP, Lukacher AE. 2006. Continuous recruitment of naïve T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med. 203: 2263-69.
- Masopust D, Ha SJ, Vezys V, Ahmed R. 2006. Prime-boost vaccination drives effector memory CD8 T cell generation. J Immunol. 177:831-9.
- Rouse BT, Masopust D. 2006. Waking up T cells in the fight against chronic infection. Trends Immunol. 27:205-7.
- Masopust D, Vezys V, Wherry EJ, Barber DL, Ahmed R. 2006. Cutting edge: gut microenvironment promotes differentiation of a unique memory CD8 T cell population. J Immunol. 176:2079-83.
- Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R. 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 439:682-87.
- Masopust D, Ahmed R. Reflections on CD8 T-cell activation and memory. 2004. Imm Res. 29:151-60.
- Masopust D, Vezys,V, Usherwood EJ, Cauley LS, Olson S, Marzo AL, Ward RL, Woodland DL, and Lefrancois L. 2004. Activated primary and memory CD8 T cells migrate to nonlymphoid tissues regardless of site of activation or tissue of origin. J Immunol. 172:4875-82.
- Masopust D, Kaech SM, Wherry EJ, Ahmed R. 2004. The role of programming in memory T cell development. Curr Opin Immunol. 16:217-25.
- Masopust D, Lefrancois, L. 2003. T cell memory: the other half the story. Microbes Infect. 5:221-6.
- Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, Ahmed R. 2003. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 4:225-34.
- Lefrancois L, Masopust D. 2002. T cell immunity in lymphoid and non-lymphoid tissues. Curr Opin Immunol. 14:503-8.
- Masopust D, Vezys V, Marzo AL, Lefrancois L. 2001. Preferential localization of effector memory cells in nonlymphoid tissue. Science. 291:2413-7.
- Masopust D, Jiang J, Shen H, Lefrancois L. 2001. Direct analysis of the dynamics of the intestinal mucosa CD8 T cell response to systemic virus infection. J Immunol. 166:2348-56.
Last updated: September 28, 2007 |
