FcR interactions do not play a major role in inhibition of experimental autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies

FcR interactions do not play a major role in inhibition of experimental autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies

Nagelkerken, L.
Haspels, I.
van Rijs, W.
Blauw, B.
Ferrant, J.L.
Hess, D.M.
Garber, E.A.
Taylor, F.R.
Burkly, L.C.
Gaubius Instituut TNO

2004

It has been demonstrated that anti-CD154 mAb treatment effectively inhibits the development of experimental autoimmune encephalomyelitis (EAE). However, although it appears to prevent the induction of Th1 cells and reactivation of encephalitogenic T cells within the CNS, little information is available regarding the involvement of alternative mechanisms, nor has the contribution of Fc effector mechanisms in this context been addressed. By contrast, efficacy of anti-CD154 mAbs in models of allotransplantation has been reported to involve long-term unresponsiveness, potentially via activation of T regulatory cells, and recently was reported to depend on Fc-dependent functions, such as activated T cell depletion through FcγR or complement. In this study we demonstrate that anti-CD154 mAb treatment inhibits EAE development in SJL mice without apparent long-term unresponsiveness or active suppression of disease. To address whether the mechanism of inhibition of EAE by anti-CD154 mAb depends on its Fc effector interactions, we compared an anti-CD154 mAb with its aglycosyl counterpart with severely impaired FcγR binding and reduced complement binding activity with regard to their ability to inhibit clinical signs of EAE and report that both forms of the Ab are similarly protective. This observation was largely confirmed by the extent of leukocyte infiltration of the CNS; however, mice treated with the aglycosyl form may display slightly more proteolipid protein 139-151-specific immune reactivity. It is concluded that FcR interactions do not play a major role in the protective effect of anti-CD154 mAb in the context of EAE, though they may contribute to the full abrogation of peripheral peptide-specific lymphocyte responses. Chemicals / CAS: Antibodies, Monoclonal; CD40 Ligand, 147205-72-9; Myelin Proteolipid Protein; Peptide Fragments; proteolipid protein 139-151; Receptors, Fc

CD40 ligand monoclonal antibody
allergic encephalomyelitis
allotransplantation
animal cell
animal experiment
animal model
cell infiltration
complement fixation
controlled study
fluorescence activated cell sorting
glycosylation
immunoreactivity
lymphocyte depletion
mouse
nonhuman
Th1 cell
Animals
Antibodies, Monoclonal
B-Lymphocytes
CD40 Ligand
Encephalomyelitis, Autoimmune, Experimental
Female
Glycosylation
Mice
Myelin Proteolipid Protein
Peptide Fragments
Receptors, Fc
T-Lymphocytes

http://resolver.tudelft.nl/uuid:bf2d5ec7-2573-4ad4-a5c2-632e3bac034d

237905

0022-1767

Journal of Immunology, 173 (2), 993-999

article