The thyroid self-antigen, thyroglobulin, induces cd4+ t cells from healthy donors to proliferate with memory cell kinetics and leads primarily to production of the regulatory cytokine, il-10

C. H. Nielsen, M. P. Galdiers, Chris Juul Hedegaard, R. G. Q. Leslie

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Objective: Thyroglobulin (TG), as auto-antigen, induces in vitro proliferation of T cells from normal individuals, with a cytokine production differing from that of
patients with autoimmune thyroid disease. We aimed to investigate whether normal TG-responsive CD4+ T cells show the reaction pattern of na¨ıve or memory
cells. For comparison, keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT) were employed as primary and secondary foreign antigens, respectively.
Results: Upon incubation with CFSE-stained normal peripheral blood mononuclear cells (PBMCs), TG elicited rapid T cell proliferation, characteristic of a secondary response. However, the TG-specific subpopulation responded with a cytokine profile quite distinct from that observed with T cells responding to TT. While TT induced pro-inflammatory cytokines (i.e. IL-2/IFN-g followed by IL-4/IL-5), TG stimulated persistent release of the regulatory cytokine, IL-10. Some donors, though, also responded with late IFN-g production, suggesting that the regulatory action of IL-10 could be over-ridden. Coating of the PBMCs with bi-specific anti- CD45/anti-IL-10 beads revealed that monocytes were the primary source of IL-10 production, as indicated by the consistent right-ward shift of the cell profile on flow-cytometry. However, counterstaining with anti-CD45RO and CD45RA revealed that TG induced IL-10 production in 3.1±1.7 memory cells per 10.000 CD4+ T cells, whereas the numbers of memory cells producing IL-10 in response to TT and KLH were non-significant (0.38 ± 0.52 and 0.52 ± 0.43 cells per 10.000 CD4+ T cells, respectively), as were the number of na¨ıve CD4+ T cells stimulated for IL-10 production by either antigen. Concordantly, depletion of CD14+ monocytes abrogated the production of IL-10. Notably, the same was true upon depletion of CD3+ T cells (p X 0.002), indicating that IL-10 production by monocyteswas regulated by T cells.
Conclusions: Our findings suggest that active peripheral tolerance towards TG may prevail in the normal population, and that IL-10 is produced by monocytes
under direct control of TG-specific memory T cells. However, the balance between pro- and anti-inflammatory cytokine responses to this auto-antigen is altered in
a sub-group of healthy individuals. The implication of these findings, in terms of predisposition of certain individuals to contract autoimmune diseases, remains
to be elucidated.
Original languageEnglish
JournalEuropean Journal of Immunology
Volume39
Issue numberSuppl 1
Pages (from-to)384
Number of pages1
ISSN0014-2980
Publication statusPublished - 2009
Externally publishedYes
Event2nd European Congress of Immunology - Berlin, Germany
Duration: 13 Sep 200916 Sep 2009
Conference number: 2

Conference

Conference2nd European Congress of Immunology
Number2
CountryGermany
CityBerlin
Period13/09/200916/09/2009

Bibliographical note

PB03/13

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