Publications (2)10.51 Total impact
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Article: Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes.
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ABSTRACT: Viral infections often gain access to the body of their host by exploiting areas of natural vulnerability, such as the semipermeable surfaces of mucosal tissues which are adapted for adsorption of nutrients and other diffusible molecules. Once the microbes have crossed the epithelial barrier, they can disperse to other tissues where eradication may not be possible. The best opportunity for successful immune intervention is immediately after infection while the pathogen is confined to a localized area of the body. Cytotoxic T lymphocytes (CTL) which reside at the site where the infection begins can make an important contribution to immunity by reducing early dissemination of the infection. Because the lungs provide easy access points for many pathogens to enter the body, they require protection from many complementary mechanisms, including pathogen-specific cytotoxic T cells. In this study we show that an enduring response to pathogen-derived peptide antigens facilitates sustained surveillance of the lungs by pathogen-specific CTL during the recovery from influenza virus infection. Our studies show that these processed peptide antigens reinforce expression of two homing receptors (CD69 and CD103) which help recently activated virus-specific CTL colonize the lungs during a mild inflammatory response. We suggest that this requirement for prolonged antigen presentation to reinforce local CTL responses in the lungs explains why protective cellular immunity quickly declines following influenza virus infection and other viral infections that enter the body via mucosal tissues.Journal of Virology 02/2011; 85(9):4085-94. · 5.40 Impact Factor -
Article: In situ imaging reveals different responses by naïve and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection.
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ABSTRACT: Pulmonary influenza infection causes prolonged lymph node hypertrophy while processed viral antigens continue to be presented to virus-specific CD8 T cells. We show that naïve, but not central/memory, nucleoprotein (NP)-specific CD8 T cells recognized antigen-bearing CD11b(+) DC in the draining lymph nodes more than 30 days after infection. After these late transfers, the naïve CD8 T cells underwent an abortive proliferative response in the mediastinal lymph node (MLN), where large clusters of partially activated cells remained in the paracortex until at least a week after transfer. A majority of the endogenous NP-specific CD8 T cells that were in the MLN between 30 and 50 days after infection also showed signs of a continuing response to antigen stimulation. A high frequency of endogenous NP-specific CD8 T cells in the MLN indicates that late antigen presentation may help shape the epitope dominance hierarchy during reinfection.European Journal of Immunology 12/2008; 38(12):3304-15. · 5.10 Impact Factor
