Autologous nucleus pulposus primes T cells to develop into lnterleukin-4-producing effector cells: An experimental study on the autoimmune properties of nucleus pulposus

Abstract

An autoimmune response to herniated nucleus pulposus has been proposed to constitute a pathophysiologie 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 (TH) cells and ending with production of autoantibodies. Activated TH cells differentiate into either T H1 cells, predominately producing proinfiammatory cytokines such as interferon γ (IFNγ) or a TH2 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 TH cells to differentiate into TH2 cells. The study was performed in a pig model allowing the exposure of NP to the immune system. To assess the polarization of TH cells the intracellular production of IFNγ and IL-4 was measured in T cells by using flow cytometry. The revealed predominant production of IL-4 together with low production of IFNγ in T cells after NP exposure to the immune system indicates that nucleus pulposus may prime TH cells to develop into IL-4-producing TH2 cells after being exposed to the immune system, for example, in association with disc herniation. © 2008 Orthopaedic Research Society.