Autologous nucleus pulposus primes T cells to develop into interleukin-4-producing effector cells: an experimental study on the autoimmune properties of nucleus pulposus.
An autoimmune response to herniated nucleus pulposus has been proposed to constitute a pathophysiologic mechanism for inducing sciatica based on the fact that nucleus pulposus under normal conditions is excluded from the development of immunological tolerance. The manifestation of an autoimmune response comprises different steps starting with antigen capture, continuing with activation of T helper (T(H)) cells and ending with production of autoantibodies. Activated T(H) cells differentiate into either T(H)1 cells, predominately producing proinflammatory cytokines such as interferon gamma (IFNgamma) or a T(H)2 subset mainly producing anti-inflammatory cytokines such as interleukin-4 (IL-4). The aim of the present study was to examine if exposure of autologous nucleus pulposus (NP) to the immune system for 3 weeks is potent enough to prime T(H) cells to differentiate into T(H)2 cells. The study was performed in a pig model allowing the exposure of NP to the immune system. To assess the polarization of T(H) cells the intracellular production of IFNgamma and IL-4 was measured in T cells by using flow cytometry. The revealed predominant production of IL-4 together with low production of IFNgamma in T cells after NP exposure to the immune system indicates that nucleus pulposus may prime T(H) cells to develop into IL-4-producing T(H)2 cells after being exposed to the immune system, for example, in association with disc herniation.
Geiss
Andrea
A
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Larsson
Karin
K
Junevik
Katarina
K
Rydevik
Björn
B
Olmarker
Kjell
K
D000818:Animals; D001323:Autoantibodies / Q000737:chemistry; D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004867:Equipment Design; D005122:Exudates and Transudates / Q000166:cytology; D007107:Immune System; D007108:Immune Tolerance; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D012585:Sciatica / Q000276:immunology / Q000473:pathology; D040521:Subcutaneous Tissue / Q000276:immunology; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001323:Autoantibodies; D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma