Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults.
Summary of "Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults."
The 2009/10 (pH1N1) pandemic highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naïve individuals. Although the last exposure to influenza was >6 months previously, the frequency and proportion of the IFN-γ-only-secreting T cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-γ-only-secreting effector-memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case-fatality-rate despite high rates of infection of the pandemic in young adults.
Affiliation
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Paddington, W2 1PG.
Journal Details
This article was published in the following journal.
Name: European journal of immunology
ISSN: 1521-4141
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22777887
- DOI: http://dx.doi.org/10.1002/eji.201242504
Medical and Biotech [MESH] Definitions
Pyloric Antrum
The region between the sharp indentation at the lower third of the STOMACH (incisura angularis) and the junction of the PYLORUS with the DUODENUM. Pyloric antral glands contain mucus-secreting cells and gastrin-secreting endocrine cells (G CELLS).
Somatostatinoma
A SOMATOSTATIN-secreting tumor derived from the pancreatic delta cells (SOMATOSTATIN-SECRETING CELLS). It is also found in the INTESTINE. Somatostatinomas are associated with DIABETES MELLITUS; CHOLELITHIASIS; STEATORRHEA; and HYPOCHLORHYDRIA. The majority of somatostatinomas have the potential for METASTASIS.
Gastrinoma
A GASTRIN-secreting neuroendocrine tumor of the non-beta ISLET CELLS, the GASTRIN-SECRETING CELLS. This type of tumor is primarily located in the PANCREAS or the DUODENUM. Majority of gastrinomas are malignant. They metastasize to the LIVER; LYMPH NODES; and BONE but rarely elsewhere. The presence of gastrinoma is one of three requirements to be met for identification of ZOLLINGER-ELLISON SYNDROME, which sometimes occurs in families with MULTIPLE ENDOCRINE NEOPLASIA TYPE 1; (MEN 1).
T-lymphocytes, Regulatory
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Insulin-secreting Cells
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
PubMed Articles
Age-dependent changes in the cellular immune response have been mainly described in CD8+ T cells, with relative sparing of CD4+ T cells. We show that in older compared to young adults, effector memory...
CD8(+) T cells play a crucial role in the clearance of intracellular pathogens through the generation of cytotoxic effector cells that eliminate infected cells and long-lived memory cells that provide...
Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis.
Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. γδ T cells, a T-cell subpopulation, are characterized by multiple biolog...
We characterized vaccine-induced cellular responses to rabies virus in naive adult volunteers. Contrary to current paradigms, we observed potent and prolonged in vitro NK cell cytokine production and...
Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival.
During viral infection, effector CD8 T cells contract to form a population of protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that control effector cell death during infec...
Clinical Trials
Heterosubtypic Immune Responses to Influenza in Older People
Vaccination is the principal means of combating epidemic and pandemic influenza. As vaccines induce relatively strain-specific and short-lived antibody responses, annual immunisation with...
Evaluation of Pandemic Influenza A (H1N1)Candidate Vaccines
This is a prospective phase I study to evaluate the safety, tolerability and immunogenicity of nine adjuvanted candidate vaccines against pandemic influenza A (H1N1) virus.
Phase II Study of Pandemic Influenza Vaccine
The World Health Organisation has warned that an influenza pandemic is inevitable. The avian influenza H5N1 virus strain is the leading candidate to cause the next influenza pandemic. This...
Immune Mobilization of Autologous Peripheral Blood Stem Cells Using Interleukin-2 and GM-CSF
We postulate that the combination of IL-2 and GM-CSF immunotherapy will efficiently mobilize autologous peripheral blood stem cells and activated immune effector cells in patients with a h...
Study of a Pandemic Influenza Vaccine
The World Health Organisation has warned that an influenza pandemic is inevitable. The avian influenza H5N1 virus strain is the leading candidate to cause the next avian influenza pandemic...
