Sequestrated Intervertebral Discs Are Mainly Infiltrated by Dendritic Cells and not Macrophages: Evidence from a Prospective Study on Patients undergoing Microdiscectomy
Authors: Geiss A. , Delank K. S. , Sobottke R. , Michael J. , Eysel P. 
Published: June 2012

Introduction Disk degeneration and mechanical compression of the spinal nerve roots by herniated disk tissue have been identified as pathogenic factors of sciatic pain. Since mechanical compression of the spinal nerve roots by herniated disk tissue has been identified as a pathogenic factor of sciatic pain, microdiscectomy has become the standard treatment for this common health problem.3 Herniated disk tissue has been suggested to induce an autoimmune response as nucleus pulposus (NP) is thought to be excluded from the establishment of immunological tolerance and hence been treated as foreign, if exposed to the immune system in association with disk herniation. From an immunological point of view manifestation of an autoimmune response comprises different steps including antigen processing through antigen-presenting cells (APCs) and differentiation of naïve T helper (TH) cells into TH effector cells. In humans, different types of APCs have been characterized including plasmacytoid dendritic cells (PDCs) and macrophages. There is an evidence suggesting that herniated disk tissue is mainly infiltrated by macrophages and T cells.2,4 The aim of the present study was to characterize the immune cells infiltrating sequestrated discs and to correlate the type of cells with postoperative outcome. Materials and Methods Total 11 patients with sequestrated disk herniations underwent neurologic examinations before microdiscectomy. Their surgically removed discs were weighted and digested for 150 minutes. After digestion the tissue clumps were separated from supernatants by centrifugation. Cells in supernatants were counted, stained with specific surface markers of macrophages (CD11c, CD14), PDCs (CD123, CD4) and activated CD4 + TH cells (CD4, CD45RO), and analyzed by flow cytometry. Recovery from deficits was assessed 2 years postoperatively by neurologic examination and SF36. Results Discs of patients with severe loss of muscle strength (grade 2 and 3) were found to be heavier (10.64g) as compared with patients displaying mild muscle weakness (grade 4 and 5). Disk infiltrates of patients with severe neurologic deficits were found to contain a high proportion of PDCs (28.01%) ( p < 0.04) but only few CD11c + CD14 + macrophages (0.31%) as compared with patients having mild motor deficits. Patients with severe neurologic deficits did not differ from patients with mild motor deficits in the proportion of activated CD4 + CD45RO +  T cells infiltrating their discs (both 5.98%). Stronger infiltration of sequestrated discs with PDCs was associated postoperatively with longer duration of complete recovery from motor deficits. Conclusion The findings of the present study do not confirm previous findings as sequestrated disk were found to be infiltrated mainly by PDCs instead of macrophages. Since disc infiltrates did comprise mainly PDCs, the current findings indicate that this APC type may initiate an autoimmune response against sequestrated discs by stimulating naïve TH cells to acquire a TH2-like effector function.1 An autoimmune response may also provide a link between disk degeneration and manifestation of sciatic pain as exposure of NP does occur during disk degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Geiss A., Larsson K., Junevik, K., Rydevik, B., Olmarker, K. Autologous nucleus pulposus primes T cells to develop into interleukin-4-producing effector cells: An experimental study on the autoimmune properties of nucleus pulposus. Journal of Orthopaedic Research 2009;27:97–103 Nerlich AG, Weiler C, Zipperer J, Narozny M, Boos N. Immunolocalization of phagocytic cells in normal and generated intervertebral discs. Spine 2002:27(22):2484–2490 Mixter WJ., Barr J. Rupture of the intervertebral disk with involvement of the spinal canal. New England Journal of Medicine 1934:211:210–215 Virri J, Grönblad M, Seitsalo S, Habtemariam A, Kääpä E, Karaharju E. Comparison of the prevalence of inflammatory cells in subtypes of disk herniations and associations with straight leg raising. Spine 2001:26(21):2311–2315