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Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2

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Waldron-Lynch, Frank  ORCID logo


The maintenance of peripheral naïve T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, post-thymic maintenance of naïve T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+ CD25− naïve T cells as defined by their levels of signal joint T-cell receptor rearrangement excision circles (sjTRECs). Here by differential gene expression analysis followed by protein expression and functional studies, we define that the naïve T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed IL-8-producing memory T cell subpopulation co-expressing CR1 and CR2 with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remains to be determined but we note that CR2 is the receptor for Epstein Barr virus, which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease.



Autoimmunity, Immunology

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American Society for Clinical Investigation
Wellcome Trust (107881/Z/15/Z)
NIHR Clinical Research Network Eastern (via Cambridge University Hospitals NHS Foundation Trust (CUH)) (unknown)
Sir Jules Thorn Charitable Trust (13/JTA (OCT2013/DR/1044))
Wellcome Trust (107212/Z/15/Z)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Wellcome Trust (105924/Z/14/Z)
Medical Research Council (G0600717)
Wellcome Trust (089989/Z/09/Z)
European Commission (241447)
Wellcome Trust (091157/Z/10/B)
European Commission Horizon 2020 (H2020) Societal Challenges (633964)
Medical Research Council (MC_UU_00002/4)
Medical Research Council (G1100114)
Medical Research Council (G0600717/1)
This work was funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007-2013) under grant agreement no.241447 (NAIMIT). The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 633964 (ImmunoAgeing).
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