The female genital mucosa is a major route of infection for HIV. This proposal will address significant gaps in knowledge regarding T cell immunobiology within the female reproductive tract. Fundamental issues, including memory CD8 and CD4 T cell differentiation, maintenance, trafficking, function, and contribution to protection will be addressed in a high-throughput tractable mouse model. Ex vivo analyses of memory T cell differentiation state, and function will be complemented by static and intravital imaging to yield a more complete anatomic picture of T cell immunobiology and APC/antigen trafficking within this complex organ system. Mechanisms underlying recently discovered functions of local memory T cells, including the ability to potentiate rapid peripheral T cell recruitment and activate the local innate immune system, will be defined. Memory T cell recirculation patterns through various compartments of the female reproductive tract will be defined by parabiosis. Contributions of local and peripheral memory T cell populations to protection against genital viral re-challenge will be assessed. These investigations will inform the development of T cell vaccines that rapidly intercept HIV upon exposure within the female reproductive tract by providing new insight into the regulation, function and protective mechanisms of cellular immunity at this site.
The female genital mucosa is a major route of infection for HIV. This proposal will address significant gaps in knowledge regarding T cell immunobiology within the female reproductive tract. Fundamental issues, including memory CD8 and CD4 T cell differentiation, maintenance, trafficking, function, and contribution to protection will be addressed in a high-throughput tractable mouse model. These investigations will inform the development of T cell vaccines that rapidly intercept HIV upon exposure within the female reproductive tract by providing new insight into the regulation, function and protective mechanisms of cellular immunity at this site.
| Beura, Lalit K; Mitchell, Jason S; Thompson, Emily A et al. (2018) Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory. Nat Immunol 19:173-182 |
| Beura, Lalit K; Wijeyesinghe, Sathi; Thompson, Emily A et al. (2018) T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells. Immunity 48:327-338.e5 |
| Steinert, Elizabeth M; Thompson, Emily A; Beura, Lalit K et al. (2018) Cutting Edge: Evidence for Nonvascular Route of Visceral Organ Immunosurveillance by T Cells. J Immunol 201:337-342 |
| Jameson, Stephen C; Masopust, David (2018) Understanding Subset Diversity in T Cell Memory. Immunity 48:214-226 |
| Beura, L K; Rosato, P C; Masopust, D (2017) Implications of Resident Memory T Cells for Transplantation. Am J Transplant 17:1167-1175 |
| Rosato, Pamela C; Beura, Lalit K; Masopust, David (2017) Tissue resident memory T cells and viral immunity. Curr Opin Virol 22:44-50 |
| Beura, Lalit K; Hamilton, Sara E; Bi, Kevin et al. (2016) Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532:512-6 |
| Schenkel, Jason M; Fraser, Kathryn A; Casey, Kerry A et al. (2016) IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells. J Immunol 196:3920-6 |
| Steinert, Elizabeth M; Schenkel, Jason M; Fraser, Kathryn A et al. (2015) Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance. Cell 161:737-49 |
| Beura, Lalit K; Anderson, Kristin G; Schenkel, Jason M et al. (2015) Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. J Leukoc Biol 97:217-25 |
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