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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 5

CR2 and CR1 are coexpressed on a subset of central memory CD4+ T cells.

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CR2 and CR1 are coexpressed on a subset of central memory CD4+ T cells.
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(A) Gating strategy and CR2 expression. Correlation of CR2 expression on central memory versus naive CD4+ T cells (B) and CR2+ central memory CD4+ T cells versus age (C) (n = 389; 371, 15, and 3 from cohorts 1–3, respectively). (D) Gating example of central memory cells sorted by CR2 expression, and gene expression analysis (NanoString). Color coding is described in Figure 4. (E) FACS analysis and compiled data of CR1 and CR2 coexpression (n = 34, age range 0–67, cohorts 1–3, paired t test). Red and gray histograms gated on CR1+ and CR1− cells, respectively. (F) Example and compiled data of IL-8 production from sorted and activated CR2+ and CR2− memory CD4+ T cells (n = 3, age range 30–44, cohort 3, paired t test).

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