Human immune responses in vivo to protein (KLH) and polysaccharide (DNP-Ficoll) neoantigens: normal subjects compared with bone marrow transplant patients on cyclosporine.

Thymus-independent (TI) and thymus-dependent (TD) primary immune responses were measured in 67 controls and 13 bone marrow transplant (BMT) recipients treated with cyclosporine (CSP) by immunizing with a synthetic antigen (DNP-Ficoll) and keyhole limpet haemocyanin (KLH). DNP-Ficoll induced similar TI antibody responses in controls and BMT recipients except that antibody levels declined much more rapidly in BMT recipients. The IgM and IgG antibodies induced by DNP-Ficoll only recognized the DNP epitope and not the Ficoll carrier. Both IgM and IgG classes of antibody showed similar TI behaviour upon immunization and re-immunization. The antibodies to DNP-Ficoll were overwhelmingly of the IgG1 subclass. The TD response to KLH evoked both delayed hypersensitivity (DH) and antibody production. DH developed at the site of immunization in 68% of controls and in 88% upon subsequent challenge with KLH. None of the BMT recipients on CSP developed DH. KLH antibody arose in 88% of controls but in only one BMT recipient on CSP. Eight BMT recipients were re-immunized with KLH 2-6 weeks after stopping CSP and only one made primary DH and antibody responses, arguing that CSP inhibited priming as well as any detectable response to KLH. The immunization procedure described has proved a sensitive and comprehensive method of quantitating human immune responses in vivo and is readily adaptable for in vitro studies.