Cellular Site of Action of Various Adjuvants in Antibody Responses to Hapten-Carrier Conjugates

Abstract

The adjuvant action of concanavalin A (Con A), Escherichia coli lipopolysaccharide (LPS), beryllium sulphate (Be salt) and Bordetella pertussis vaccine have been analyzed in a system measuring humoral immune responses to hapten-carrier conjugates in mice. For the definition of the cellular locus of their action, the effect of these adjuvants on adoptive secondary anti-hapten antibody responses was studied. Spleen cells from 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH) primed donors, which normally fail to develop adoptive secondary anti-DNP responses to a heterologous conjugate such as DNP-bovine γ-globulin (BGG), can be stimulated to do so when an appropriate dose of adjuvant is administered with DNP-BGG. The capacity for the adjuvants employed to exert this effect requires the presence of thymus-derived (T) lymphocytes, since depletion of such cells by treatment of the donor cell inoculum with anti-θ serum and complement in vitro before adoptive transfer abrogates the response to DNP-BGG plus adjuvant. Moreover, evidence is presented which demonstrates that these substances exert their adjuvant action through the small number of unimmunized BGG-specific T lymphocytes in the donor cell inoculum. This conclusion derives from the failure of adjuvants to augment adoptive secondary anti-DNP responses to the DNP derivative of a non-immunogenic copolymer of d-glutamic acid and d-lysine for which there are few or no specific, functional T cells.