RT Journal Article
SR Electronic
T1 Complement receptor 2 and IL-8 production identifies in adults and neonates naïve T cells recently arising from the thymus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 059535
DO 10.1101/059535
A1 Marcin L Pekalski
A1 Arcadio Rubio García
A1 Ricardo C Ferreira
A1 Daniel B Rainbow
A1 Deborah J Smyth
A1 Meghavi Mashar
A1 Jane Brady
A1 Natalia Savinykh
A1 Xaquin Castro Dopico
A1 Sumiyya Mahmood
A1 Simon Duley
A1 Helen E Stevens
A1 Neil M Walker
A1 Antony J Cutler
A1 Frank Waldron-Lynch
A1 David B Dunger
A1 Claire Shannon-Lowe
A1 Alasdair J Coles
A1 Joanne L Jones
A1 Chris Wallace
A1 John A Todd
A1 Linda S Wicker
YR 2016
UL http://biorxiv.org/content/early/2016/06/17/059535.abstract
AB The maintenance of a diverse, naïve T cell repertoire arising from the thymus (recent thymic emigrants: RTEs) is critical for health1. Recent studies have reported a unique naïve CD4+ T cell subset in neonates and early childhood characterized by IL-8 production2,3. Here we demonstrate that IL-8 production is a characteristic feature of RTEs in adults, children and neonates and that a hallmark of these cells is the expression of complement receptor 2 (CR2) and the preferential production of IL-8 after activation. Although decreasing in number with age due to thymic involution and homeostatic expansion of naïve CD4+ T cell in humans4, CR2+ RTEs persist into old age, have the highest levels of T cell receptor excision circles (TRECs), co-express complement receptor 1 (CR1), TLR1 and produce IL-8 upon TCR stimulation. We have observed these phenotypes in the vast majority of cord blood naïve CD4+ T cells and in newly-generated naïve T cells appearing during reconstitution of the immune system in adults depleted of T cells through treatment for multiple sclerosis. A memory subset of CR2+ CD4+ T cells expressing high levels of CR1 and producing IL-8 following activation was also discovered, consistent with the hypothesis that RTE-specific gene expression confers a functional competence retained by particular memory T cells possibly because of their complement-dependent reactivity to pathogens. We suggest that assessing CR2 expression on naïve CD4+ T cells will give a measure of thymic function during aging of the immune system and in a number of clinical situations including bone marrow transplantation5, HIV infection6, and immune reconstitution following immune depletion7 or chemotherapy8.