Effect of factor VIII concentrate on antigen-presenting cell (APC)/T-cell interactions in vitro: relevance to inhibitor formation and tolerance induction

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dc.contributor.authorHodge, G.
dc.contributor.authorHan, P.
dc.date.issued2000
dc.description.abstractInhibitor formation in patients with haemophilia receiving factor VIII (FVIII) concentrate is a common problem requiring tolerance induction therapy. Immune tolerance is dependent on defective T cell/antigen-presenting cell (APC) interactions and inhibitor antibody formation is associated with effective T-cell/B-cell interaction. We studied the expression of the cell-surface molecules involved with these interactions using multiparameter flow cytometry and a whole blood stimulation assay-phytohaemaglutinin (PHA) to activate T cells and Escherichia coli lipopolysaccharide (LPS) to activate monocytes and B cells. Up-regulation of T-cell co-stimulatory receptors CD11a, CD40 ligand (CD40L) and CTLA4 were inhibited in a dose-dependent manner by plasma-derived (pd)FVIII, but CD28 was unchanged. Up-regulation of monocyte and B-cell co-stimulatory ligands CD4O, B7-1 (CD80) and B7-2 (CD86) were also inhibited in a dose-dependent manner by pdFVIII, but LFA-3 (CD58) was unchanged. The combined inhibitory effect of prednisolone, an immunosuppressive agent used in several tolerance induction protocols, with pdFVIII on co-stimulatory molecules, was additive. There was no significant alteration in T-cell/APC adhesion or co-stimulatory molecules noted in the presence of recombinant (rh)FVIII concentrate. The inhibitory effect of pdFVIII on molecules involved in interaction between T cells and APCs may result in immune tolerance in recipients of pdFVIII concentrate. The inhibitory effect of pdFVIII on CD40/CD40L up-regulation may result in defective antibody formation. We now provide evidence that the use of pdFVIII, through interfering with APC/T-cell interactions, may be more appropriate than rhFVIII for tolerance induction.
dc.description.statementofresponsibilityHodge, G. ; Han, P.
dc.identifier.citationBritish Journal of Haematology, 2000; 109(1):195-200
dc.identifier.doi10.1046/j.1365-2141.2000.01994.x
dc.identifier.issn0007-1048
dc.identifier.issn1365-2141
dc.identifier.urihttp://hdl.handle.net/2440/7066
dc.language.isoen
dc.publisherBlackwell Science Ltd
dc.source.urihttps://doi.org/10.1046/j.1365-2141.2000.01994.x
dc.subjectB-Lymphocytes
dc.subjectAntigen-Presenting Cells
dc.subjectT-Lymphocytes
dc.subjectHumans
dc.subjectHemophilia A
dc.subjectPrednisolone
dc.subjectFactor VIII
dc.subjectMembrane Glycoproteins
dc.subjectLymphocyte Function-Associated Antigen-1
dc.subjectRecombinant Proteins
dc.subjectImmunosuppressive Agents
dc.subjectAntigens, CD
dc.subjectFlow Cytometry
dc.subjectStatistics, Nonparametric
dc.subjectLymphocyte Activation
dc.subjectImmune Tolerance
dc.subjectB7-2 Antigen
dc.titleEffect of factor VIII concentrate on antigen-presenting cell (APC)/T-cell interactions in vitro: relevance to inhibitor formation and tolerance induction
dc.typeJournal article
pubs.publication-statusPublished

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