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Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2
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
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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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 4

CR2+ naive CD4+ T cells have a unique molecular signature.

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CR2+ naive CD4+ T cells have a unique molecular signature.
(A) Volcano p...
(A) Volcano plots of differences in gene expression (NanoString platform) between CR2+ versus CR2− naive CD4+ T cells (gating strategy shown as insert) ex vivo and after activation (anti–CD3/CD28). Genes expressed at a higher or lower level in CR2+ cells have red or blue symbols, respectively. Underlined genes have lower expression after activation. Genes in boxes are from the RNA-seq platform (n = 4 adult donors from cohorts 1 and 3). (B) Ex vivo CR1 protein expression on CR2+ and CR2− cells (n = 34, age range 0–67, cohorts 1–3, paired t test). Red and gray histograms gated on CR1+ and CR1− cells, respectively. (C) Representative histograms and compiled frequencies of cytokine production following activation of CR2+ and CR2− cells sorted from CD31+CD25− naive CD4+ T cells (n = 3, age range 30–44, cohort 3, paired t test). (D) Representative histograms of IL-8 production from isolated CD4+ T cells following activation with PMA and ionomycin. Compiled data of percentage IL-8+ cells out of naive (CD45RA+) CD4+ T cells (unpaired t test, n = 3 cord bloods from cohort 3, 4 multiple sclerosis [MS] patients 6 to 9 months after treatment, 3 MS patients >10 years after treatment. Correlation of percentage IL-8+ cells (following activation) and percentage CR2+ cells (assessed prior to activation) in the MS patients (n = 7).

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