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ImmunologybioRxiv

Recent thymic emigrants produce antimicrobial IL-8, express complement receptors and are precursors of a tissue-homing Th8 lineage of memory cells

M. L. Pekalski, A. Rubio Garcia, R. C. Ferreira, D. B. Rainbow, D. J. Smyth, M. Mashar, J. Brady, N. Savinykh, X. Castro Dopico, S. Mahmood, S. Duley, H. E. Stevens, N. M. Walker, A. J. Cutler, F. Waldron-Lynch, D. B. Dunger, C. Shannon-Lowe, A. J. Coles, J. L. Jones, C. Wallace, J. A. Todd, L. S. Wicker

Abstract

The adaptive immune system utilizes multiple mechanisms linked to innate immune cell functions to respond appropriately to pathogens and commensals. Here we discover further aspects of this connectivity by demonstrating that naive T cells as they emerge from the thymus (recent thymic emigrants, RTEs) express complement receptors (CR1 and CR2), the bacterial pathogen recognition receptor TLR1 and an enzyme that deactivates bacterial lipopolysaccharide (AOAH) and following activation secrete the anti-microbial cytokine IL-8. CR2+ naive T cells also express a selection of genes associated with tissue migration, consistent with the hypothesis that following emigration from the thymus RTEs seed peripheral compartments where some pursue their anti-microbial potential by becoming IL-8-producing CR2+ memory cells while others undergo homeostatic expansion. CR2+ naive and memory cells are abundant in children but decrease with age, coinciding with the involution of the thymus. The ability of CR2, which is also a receptor for Epstein-Barr Virus (EBV), to identify recent thymic emigrants will facilitate assessment of thymic function during aging and aid investigations of multiple clinical areas including the occurrence of T cell lymphomas caused by EBV.

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02 /Specification & Classification

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