Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

Open Access

In vivo preactivated autoreactive Th cells in healthy individuals

  • A Radbruch1,
  • S Nitsch1,
  • B Holzknecht1,
  • E Gromnica-Ihle1,
  • S Schneider1,
  • F Hiepe1 and
  • A Thiel1
Arthritis Research & Therapy20013(Suppl 2):P058

DOI: 10.1186/ar227

Received: 15 January 2001

Published: 26 January 2001

The direct analysis of autoantigen-specific Th-cells has been hampered so far by the lack of appropiate methods to directly determine their frequency or functional capabilities. We have applied a set of new techniques to directly identificate and analyze autoantigen-specific T-cells in both affected and healthy people according to their effector functions (e.g. effector cytokine production) after provocation with antigen.

We have used these technologies to analyze Th-cells specific for SLE-associated autoantigens, in particular nucleosomes and the ribonucleoprotein La. Suprisingly, in vivo pre-activated autoantigen-specific Th-cells secreting IFNgamma and TNFalpha, could be detected not only in SLE-patients, but also in normal healthy persons, with frequencies ranging from 0.02% to 0.1%. Preactivation of these cells in vivo was confirmed by the fact that they expressed CD45RO but not CD45RA. Some of them had down-regulated expression of CD45RB and CD27. We also detected in healthy donors in vivo preactivated Th-cell specific for the self-antigen alphaB-Cristallin, a small heat shock protein. Up to 0.5% of peripheral Th cells specifically react with IFNgamma secretion upon short term stimulation, a hallmark of a recall response, i.e. in vivo preactivation.

The fact that in vivo pre-activated, autoantigen-specific Th-cells can be detected at comparable frequencies and with similar cytokine secretion patterns in blood of normal persons and patients suffering from a disease in which such Th cells are suspected to play a pivotal role, points to mechanisms other than central and peripheral tolerance that control the initiation of those autoimmune reactions.

Authors’ Affiliations

(1)
Deutsches Rheuma-Forschungszentrum Cell Biology

Copyright

© BioMed Central Ltd 2001

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