Immunogenicity of bacterial carbohydrates: cholera toxin modulates the immune response against dextran B512.
Native dextran B512 is a T-cell-independent (TI) antigen. By conjugating low molecular weight (MW) dextran to protein, a T-cell-dependent (TD) response against dextran can be obtained. We have previously reported the effects of native dextran and two different protein-dextran conjugates on the immune system. While one type of conjugate induced an optimal TD response, the other conjugate ('suboptimal') evoked a response more similar to that induced by native dextran, i.e. with little immunoglobulin class switch and with a secondary response of similar magnitude to the primary response. In order to investigate if it was possible to augment the anti-dextran response we examined the effects of cholera toxin (CT) in our dextran model system. CT is a potent mucosal, as well as systemic, adjuvant with effects on T cells, B cells and antigen-presenting cells. We show that CT is a very efficient adjuvant for both the TD and TI forms of dextran. A major increase in IgM and IgG anti-dextran antibody production was detected after administration of CT together with the conjugates compared with a conventional alum adjuvant. The effect was most pronounced for the suboptimal TD conjugate. CT was also able partially to abrogate the unresponsiveness to dextran in the TI type 2 (TI-2) non-responder strain CBA/N. CT was also found to be a very potent adjuvant for native dextran, secondary IgM levels were enhanced eightfold by the co-administration of CT. Furthermore CTB-Dx, which is a conjugate of the non-toxic part of CT and low MW, non-immunogenic dextran, elicited an anti-dextran response in nude mice. Collectively, our data show that it is possible to improve the immunogenicity of both TD and TI forms of a carbohydrate by co-administration of CT. This is indicative of two components of the adjuvant effect, one could enhance antigen presentation and costimulation of T cells and the other could have a direct stimulatory effect on B cells.
Sverremark
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Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Fernandez
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C
D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology*; D003911:Dextrans / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D003911:Dextrans; D007136:Immunoglobulins; D002772:Cholera Toxin