Mice with the xid Mutation Lack the Regulatory Antibodies That Are Necessary for the Induction of Contrasuppression

We present evidence that mice with X-linked immunodeficiency (xid) lack circulating regulatory immunoglobulin (reg Ig) necessary for control of antigen-specific suppressor T cells (Ts). Previous work demonstrated that reg Ig is one component of a serum factor that blocks Ts activity, thereby allowing appropriate antibody responses in vivo and in vitro. These factors are referred to as contrasuppressor factors (CSF). CSF are detected in the serum of mice 3-6 hr after immunization with SRBC or can be generated in vitro by combining normal mouse serum with supernatants of macrophage-T cell cocultures (Mّ-T sup). Data presented here demonstrate that CSF were not detectable in the serum of immunized xid mice. Serum from xid mice or affinity-purified serum IgG and IgA failed to generate CSF in vitro, indicating a lack of reg Ig in xid serum. However, xid T cells could block suppression of isotype-specific antibody responses in vitro when incubated with functional CSF containing Mّ-T sup and CBA/J reg IgG or IgA. Similarly, xid macrophages showed no defect in generation of functional Mّ-T sup in vitro. Finally, CBA/J Vicia villosa adherent (Vv) T cells that were incubated with in vitro generated CSF allowed anti-SRBC responses in vivo, when adoptively transferred into xid mice, prior to SRBC immunization. These responses were comparable to those of normal CBA/J mice immunized with SRBC. Similarly, xid mice that received xid T cells treated with CSF and were immunized with SRBC generated good anti-SRBC PFC responses. These studies provide strong evidence that xid mice lack circulating reg Ig resulting in defective CSF and consequently low antibody responses to SRBC, due to dominant T. activity.