Altered antigen-presentation in the induction of the in-vitro antigen-specific T helper cell function in patients with chronic granulomatous disease.
Phagocytic cells of patients with chronic granulomatous disease (CGD) are severely impaired in the killing process, on the basis of defective oxygen metabolism. In this study we investigated the antigen-presenting function of monocytes (i.e. adherent cells) of CGD patients. Adherent cells of CGD patients were investigated for their capacity to present ovalbumin (OA) in such a way that T helper cells are activated and OA-specific IgM-plaque forming cells (PFC) are generated. The results showed that the dose of OA required for optimal PFC responses was 20-25 times higher than the dose of antigen which is necessary for induction of PFCs from peripheral blood mononuclear cells of normal donors. We could show that the CGD monocytes were responsible for the observed shift which indicates peculiar antigen-presenting capacities. The finding could be mimicked in normal donors by treating adherent cells with phenylbutazone, a drug known to interfere with oxygen-dependent degradation of micro-organisms. Moreover, our results suggested that CGD monocytes and phenylbutazone-treated monocytes of normal donors absorb OA but do not re-express the processed antigen on the membrane. We conclude that our system used to study antigen presentation allowed the discovery of altered antigen presentation of CGD monocytes most probably on the basis of defective antigen processing. However, antigen presentation is not entirely absent, since relatively high doses of OA induced normal PFC responses in CGD mononuclear cells.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002448:Cell Adhesion; D006105:Granulomatous Disease, Chronic / Q000276:immunology*; D006462:Hemolytic Plaque Technique; D006801:Humans; D010047:Ovalbumin / Q000276:immunology; D010653:Phenylbutazone / Q000494:pharmacology; D011402:Pronase / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D010047:Ovalbumin; D011402:Pronase; D010653:Phenylbutazone