© 2003 Blackwell Publishing Ltd 39 Parasite Immunology , 2003, 25, 39–44 Blackwell Publishing Ltd. RESEARCH NOTE Antibody isotype regulation in schistosomiasis Differential production in vitro of antigen specific IgG1, IgG3 and IgA: a study in Schistosoma haematobium infected individuals LYDIE BÉNIGUEL 1 , TAMSIR O. DIALLO 2 , FRANCK REMOUÉ 2 , DAVID L. WILLIAMS 3 , FABRICE COGNASSE 1 , NICOLE CHARRIER-MZE 4 , ABDOULAYE A. N’DIAYE 4 , RONALD PERRAUT 5 , MONIQUE CAPRON 2 , GILLES RIVEAU 2 & OLIVIER GARRAUD 1 1 GIMAP, EA 3064, Université de Saint-Etienne, Faculté de Médecine, 15, rue Ambroise Paré, 42023 Saint-Etienne cedex 2, France, 2 INSERM U547, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019, Lille Cedex, France, 3 Department of Biological Sciences, Illinois State University, Normal, IL 61790-4120, USA, 4 Programme ESPOIR, Région Médicale de Saint-Louis-du-Sénégal, BP 394, Saint-Louis-du-Sénégal, Sénégal, 5 Laboratoire d’Immunologie, Institut Pasteur, BP 220, Dakar, Sénégal SUMMARY This study has evaluated the individual control of isotype pro- duction and the influence of external signals that can be experimentally provided in vitro, in antibody responses to two different recombinant Schistosoma antigens (Sh28GST and TPx-1). Peripheral blood mononuclear cells or enriched B cell fractions obtained from S. haematobium infected Senegalese adults were induced to terminal differentiation in vitro. The production of antibody to either antigen was donor-dependent and for each donor it was antigen-dependent. Differentiation to IgG1 and IgG3 production, and possibly IgA, specific to these conserved parasite antigens could be regulated differen- tially in vitro. Exogenous IL-2 and IL-10 or IL-10 and TGF- β led to the production of specific IgG3 or IgG1 and/or IgA, respectively. This is the first report on such experimentally induced differential regulation of antigen-specific IgG1 and IgG3. This may have implications in designing protocols for protein based-vaccinations aiming at eliciting antibody responses of certain protective-type isotypes. INTRODUCTION Immuno-epidemiological studies have established the fun- damentals of antibody (Ab)-based protection, particularly with respect to parasitic infections that generate protective Ab responses with or without cellular mechanisms (1). Experimental studies derived from immuno-epidemiological surveys have defined important mechanisms frequently involving an isotype restriction of effector mechanisms of protection (2). Most vaccine perspectives to these parasite infections are based on the assumption that the vaccine can- didate is expected to favour the production of Abs of the isotypes that have the best chances to be effective. However, there is no experimental evidence yet that immunization with parasite antigens (Ags) can produce an Ab response of a given class/subclass (isotype). In chronic human Schistosoma ssp. infections, there is an elevation of Abs to parasite-derived Ags and age- and exposure- dependent acquired immunity is correlated with a balance of induced isotype responses (reviewed in 3–5). In particular, the protective role of IgE (6) and blocking effects of IgG4 and IgM (7) have been proposed. Infected adults treated with Praziquantel® developed specific IgG3 and/or IgA to the Schistosoma mansoni (Sm)-28GST vaccinal Ag (8) that appeared to play a crucial role in acquired immunity against re-infection (9). Schistosoma haematobium (Sh)-infected Senegalese were shown to have elevated anti-Sh28GST IgG3, IgA and IgE Abs, relative to IgG1 (10). Unbalanced isotypic responses, with predominant IgG1, IgA, and then IgG3 relative to IgE and IgG4, against Schistosoma mansoni thioredoxin peroxidase (TPx) have also been noted (Remoué et al. unpublished data). Studies aimed at examining more precisely the mechanisms of Ab isotype production in response to given Schistosoma Ags are needed. The present descriptive investigation has been undertaken to evaluate the respective roles of the Correspondence: Dr O. Garraud, GIMAP, EA 3064, Université de Saint-Etienne, Faculté de Médecine, 15, rue Ambroise Paré, 42023 Saint-Etienne cedex 2, France (e-mail: Olivier.Garraud@univ-st-etienne.fr). L. Béniguel and T. O. Diallo contributed equally to this work. Received: 22 July 2002 Accepted for publication: 28 January 2003