Immunoregulatory role of Ig isotypes. II. Activation of cells that block induction of contact sensitivity responses by antibodies of IgG2a and IgG2b isotypes.

Abstract

The influence that the isotype of Ag-specific antibody has on the induction of contact hypersensitivity (CS) has been investigated. Injection (i.v.) of mice with haptenated peritoneal exudate cells (PEC) pretreated with anti-hapten mAb of the IgG2a and IgG2b isotypes results in the activation of Ag-specific afferent acting Ts cells (Ts-aff). These suppressor cells are not generated when animals are injected with anti-hapten antibodies of other isotypes. The Ts-aff cells function to inhibit the generation of CS responses when injected into naive animals. Suppression is due to the induction of both Lyt-1+,2- I-J+ and Lyt-1-,2+ I-J+ T cells, both of which adhere to the lectin Vicia villosa. Attachment of both TNP and 4-ethoxymethylene-2-phenyloxazolone haptens to the same PEC, followed by treatment with an IgG2a anti-TNP antibody, generates Ts-aff cells specific for both 4-ethoxymethylene-2-phenyloxazolone and TNP. The MHC haplotype of the PEC is irrelevant, as allogeneic PEC will also induce Ts-aff cells when injected by using an identical protocol. Ts-aff cells cannot be generated in B cell-depleted mice, nor does the Ts-aff cells generated in normal mice suppress CS responses in B cell-depleted mice. These results show that Ag-antibody complexes bound on the surface of a PEC can induce potent afferent suppression in vivo. A possible general role for antibody isotypes in directing regulatory activities is discussed.