Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 5; pp. 939 - 948
• Main Authors: Slütter, Bram, Pewe, Lecia L, Kaech, Susan M, Harty, John T
• Format: Journal Article
• Language: English
• Published: United States 14.11.2013
• Subjects: Adoptive Transfer; Animals; Bronchoalveolar Lavage Fluid - immunology; CD8-Positive T-Lymphocytes - chemistry; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - transplantation; Chemotaxis, Leukocyte; Dendritic Cells - immunology; Immunization, Secondary; Immunologic Memory; Influenza A virus - immunology; Influenza A virus - pathogenicity; Influenza Vaccines - immunology; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; Lung - immunology; Lymph Nodes - immunology; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Receptor, Interferon alpha-beta - deficiency; Receptors, CXCR3 - biosynthesis; Receptors, CXCR3 - deficiency; Receptors, CXCR3 - genetics; Receptors, CXCR3 - physiology; Respiratory System - immunology; STAT4 Transcription Factor - physiology; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Vaccination
• ISSN: 1097-4180
• DOI: 10.1016/j.immuni.2013.09.013

Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV.