CD30 Molecule, the Immune System and Multiple Sclerosis. CD30 the still unknown molecule involved in the cell contact-dependent suppression of T cells by dendritic cells, which mediated signals responsible for maintainig the physiological balance between: dendritic and T regulatory cells, the immune responses and central and peripheral tolerance.

Objectives: on the basis of our own and other research on the CD30 molecule, we hypothesized that CD30 may be the unknown molecule involved in the cell contact-dependent suppression of T regulatory cells (Trs) by regulatory dendritic cells (rDCs). Trs are responsible for maintaining the physiological balance between TH1/TH2/TH3 immune responses and central and peripheral tolerance. Thus DC CD30-mediated signals are of key importance both in the initial phase of immune response as well as in maintaining the physiological balance between TH1/TH2/TH3 immune responses. We believe that abnormal CD30 signalling can lead to the generation of autoimmune diseases such as Multiple Sclerosis (MS) and hence, in addition to substantiating the hypothesis above, our objective was also to clarify the immunopathological mechanisms involved in MS and the causes of immunosuppressive drug failure. Methods: we determined network interactions between sCD30, sBcl2 and TH1/TH2/TH3 cytokines (IL12p70, IL12p40, IL10 and TGF?) in immature (I) DC and DC culture supernatants in IFN?-1a treated and untreated relapsing-remitting MS (RRMS) patients. TH1/TH2/TH3 cytokine networks in whole blood culture supernatants in PHA activation conditions were also studied. Results: our overall results, in support of our hypothesis, indicate that CD30 is involved in the cell contact-dependent suppression of TH cells by regulatory IDCs (rIDCs), and rDCs and that this contact-dependent suppression is indispensable for the generation of TGF??producing Tr (TH3) subsets. Alterations at this level were found in untreated patients, while IFN?-1a treatment was found to restore the physiological mechanisms by increasing suppressive (sp-) IDC and sp-DC activity (IL10) resulting in a lowering of sCD30 levels, re-establishment of CD30-mediated signals and equilibrium between type1- and type2-like immune response (rICD1/rIDC2 and rDC1/rDC2). Consequently, CD30 being responsible for the balance between Tr1/Tr2, re-establishes equilibrium between immune responses and central and peripheral tolerance. However it also appears that IFN??1a treatment is responsible for the in vivo suppression of patient TH1-DC functions which involve the induction of Tr1s for the deletion of self aggressive cells in the immune response in activation conditions, and this may explain the cause of immunosuppressive drug failure. Conclusion: CD30 mediates signals for a key mechanism involving dendritic and T regulatory cells responsible for maintaining the physiological balance between immune responses and central and peripheral tolerance. - Multiple Sclerosis is the result of alterations at this level, however IFN?-1a treatment is partially successful in restoring the physiological mechanisms affected. Further study can lead to new ways of identifying methods for more effective prevention and treatment of immunopathological conditions such as autoimmune diseases, transplant rejection, allergy and tumor.