Vaccines have led to many of the world's greatest public health triumphs, but many deadly viruses, such as HIV, elude the best efforts to develop effective vaccines. An improved understanding of how the immune system operates during a viral infection is critical to designing successful anti-virus vaccines, particularly those designed to elicit T cells, which have the ability to kill virus infected cells before progeny viruses are produced. Many vaccines are delivered in the skin or muscle, where they initiate immune responses in draining lymph nodes. To better understand how live virus vaccines activate T cells, we are using a multiphoton microscope to visualize the interaction of T cells with viruses in living mice. This year our studies have demonstrated distinct locations and effector roles for innate and adaptive immune cells in clearing a poxvirus skin infection.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$748,434
Indirect Cost
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State
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Zip Code
Hickman, Heather D; Reynoso, Glennys V; Ngudiankama, Barbara F et al. (2015) CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells. Immunity 42:524-37
Hickman, Heather D (2015) Immunology. There goes the macrophage neighborhood. Science 347:609-10
Hickman, Heather D; Yewdell, Jonathan W (2013) Going Pro to enhance T-cell immunogenicity: easy as ýý? Eur J Immunol 43:2814-7
Hickman, Heather D; Reynoso, Glennys V; Ngudiankama, Barbara F et al. (2013) Anatomically restricted synergistic antiviral activities of innate and adaptive immune cells in the skin. Cell Host Microbe 13:155-68
Hickman, Heather D; Li, Lily; Reynoso, Glennys V et al. (2011) Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. J Exp Med 208:2511-24
Hickman, Heather D; Bennink, Jack R; Yewdell, Jonathan W (2009) Caught in the act: intravital multiphoton microscopy of host-pathogen interactions. Cell Host Microbe 5:13-21