Immune activation in the interface between innate immunity and adaptive response:in vitro studies and therapeutical implications
In multiple sclerosis (MS), as well as in other putatively T cell mediated diseases, much attention has been devoted to possible dysregulations at the level of the adaptive immune response, with particular emphasis on the search for potential T lymphocyte autoantigens. These investigations have been, in many cases, unrewarding. One reason may be that T cells are not the key players in self-nonself discrimination: T cell receptors (TCR) have randomly generated specificities that, for this reason, cannot determine the origin and biological context of their ligands . It is becoming increasingly evident that this task is better carried out by the innate immune system that relies on germline-encoded receptors which bind to invariant molecules shared by large groups of microorganisms. These structures (techoic acids, lipopolysaccharides (LPS), double-stranded RNA, mannans) are therefore readily recognized as markers of infection by the innate immune system that instructs the adaptive response accordingly . Based on this evidence, it is now clear that the correct functioning of innate and adaptive immunity as well as their balanced interaction are essential for a physiological immune response . This has prompted much of the recent research focused on the interface between these two arms of the immune system in autoimmunity.
KeywordsMultiple Sclerosis Innate Immune System Multiple Sclerosis Plaque Extracellular Matrix Glycoprotein Cell Mediate Disease
Unable to display preview. Download preview PDF.
- 4.Steel DM, Whitehead AS (1994) The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 15: 81–88Google Scholar
- 5.Xu L, Badolato R, Murphy WJ, Longo DL, Anver M, Hale S, Oppenheim JJ, Wang JM (1995) A novel biologic function of serum amyloid A (SAA). Induction of T lymphocyte migration and adhesion. J Immunol 155: 1184–1190Google Scholar
- 6.Preciado-Patt L, Hershkovitz R, Fridkin M, Lider O (1996) Serum amyloid A binds specific extracellular matrix glycoproteins and induces adhesion of resting CD4 T cells. J Immunol 156: 1198–1205Google Scholar
- 8.Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 179: 973–984PubMedCrossRefGoogle Scholar
- 9.Allegretta M, Nicklas JA, Sriram S, Albertini RJ (1990) T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247: 718721Google Scholar
- 10.Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA (1992) y8 T cell receptor in acute multiple sclerosis lesions. Proc Natl Acad Sci USA 89: 4588–4592Google Scholar
- 14.Freedman MS, Ruijs TCG, Selin LK, Antel JP (1991) Peripheral blood y-8 T cells lyse fresh human brain-derived oligodendrocytes. Ann Neurol 30: 794800Google Scholar
- 17.Poggi A, Zocchi MR, Costa P, Ferrero E, Borsellino G, Placido R, Galgani S, Salvetti M, Gasperini C, Ristori G, Brosnan CF, Battistini L (1999) IL-12mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V82+ TCRy+ T lymphocytes from healthy donors and multiple sclerosis patients. J Immunol (in press)Google Scholar
- 19.Lewin B (1993) Genes V. Oxford University, OxfordGoogle Scholar
- 22.Ristori G, Buttinelli C, Pozzilli C, Fieschi C, Salvetti M (1999) Microbe exposure, innate immunity and autoimmunity. Immunol Today (in press)Google Scholar
- 24.Pozzilli P, on behalf of the IMDIAB Group (1997) BCG vaccine in insulin-dependent diabetes mellitus. Lancet 349: 1520–1521Google Scholar
- 25.Miller DH, Alpert PS, Barkhof F, Frances G, Frank JA, Hodgkinson S, Lublin FD, Paty DW, Reingold SC, Simon J (1996) Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. US National MS Society Task Force. Ann Neurol 39: 6–16Google Scholar