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Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2
Marcin L. Pekalski, … , John A. Todd, Linda S. Wicker
Marcin L. Pekalski, … , John A. Todd, Linda S. Wicker
Published August 17, 2017
Citation Information: JCI Insight. 2017;2(16):e93739. https://doi.org/10.1172/jci.insight.93739.
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Research Article Immunology

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

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Abstract

The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25− naive 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 naive 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 an IL-8–producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain 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.

Authors

Marcin L. Pekalski, Arcadio Rubio García, Ricardo C. Ferreira, Daniel B. Rainbow, Deborah J. Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E. Stevens, Neil M. Walker, Antony J. Cutler, Frank Waldron-Lynch, David B. Dunger, Claire Shannon-Lowe, Alasdair J. Coles, Joanne L. Jones, Chris Wallace, John A. Todd, Linda S. Wicker

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Figure 1

Gene expression profiling of 4 naive CD4+ T cell subsets identify age-related molecular signatures.

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Gene expression profiling of 4 naive CD4+ T cell subsets identify age-re...
(A) Gating strategy defining human naive CD4+ T cells; naive T cells were further stratified by CD31 and CD25. Representative examples (from n = 391; 371, 15, and 5 from cohorts 1–3, respectively; see Methods for details) of naive CD4+ T cells. (B) The proportion of naive CD4+ T cells as a function of age (color coding shown above graph). (C) Volcano plot of differences in gene expression (microarray platform) between CD31+CD25− and CD31–CD25− naive CD4+ T cells; red and blue symbols for genes with higher and lower, respectively, expression in CD31+CD25− naive CD4+ T cells (n = 20, cohort 1).

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