Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes

Abstract

Background: MHC class I-restricted CD8 + cytotoxic T lymphocytes (CTL) are thought to play a major role in clearing virus and promoting recovery from influenza infection and disease. This has been demonstrated for clearance of influenza virus from the lungs of infected mice. However, human influenza infection is primarily a respiratory mucosal infection involving the nasopharynx and tracheobronchial tree. The role of CD8 + CTL directed toward the influenza nucleoprotein (NP) in defense against influenza virus infection at the respiratory mucosa was evaluated in two separate adoptive transfer experiments.

Histopathology and growth kinetics of influenza viruses (H1N1 and H3N2) in the upper and lower airways of guinea pigs

“…Since both HK/68 and PR8 have been widely used in animal model studies, our findings allow comparison of IAVinduced airway disease in guinea pigs with published results on airway lesions in mice and ferrets (Mbawuike et al, 2007;Sanford & Ramsay, 1987). For these IAV strains, infected guinea pigs showed somewhat more severe nasal and lung disease than have been previously reported for mice (Iwasaki et al, 1999;Chong et al, 2008).…”

The Magnitude of Local Immunity in the Lungs of Mice Induced by Live Attenuated Influenza Vaccines Is Determined by Local Viral Replication and Induction of Cytokines

“…Nasalassociated lymphoid tissue (NALT) was shown to be the site of induction of mucosal responses (47). CD8 ϩ T cells induced either by vaccination or adoptive transfer can mediate viral clearance in the respiratory tract in the absence of humoral immunity (12,15,24,30,32). Although the contribution of CD8 ϩ T cells to protection from influenza virus infection in humans is less clear than in mice, the induction of CD8 ϩ T cells by LAIVs has been demonstrated in children (23), and evidence suggestive of heterosubtypic immunity during the 1957 pandemic was presumed to be mediated by CD8 ϩ T cells (18).…”

Seasonal influenza infection and live vaccine prime for a response to the 2009 pandemic H1N1 vaccine

“…Following a heterologous infection, there was an expansion of these CD8 + T cells in lungs with immediate effector functions such as the production of antiviral cytokines. The contribution of CD8 + T cells to viral clearance from the lungs has been demonstrated in a number of studies, using adoptive transfer, depletion of CD8 + T cells, or CTL-inducing vaccines (34)(35)(36)(37)(38)(39). CD8 + T cells can mediate viral clearance from the respiratory tract by lysing target cells following exocytosis of granules containing perforin and granzymes (40).…”