Tolerance to aggregated human IgG but not ovalbumin can be induced by concurrent administration of depleting or non‐depleting anti‐L3T4 monoclonal antibodies

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Abstract
Tolerance to soluble antigens has previously been shown to occur in mice if anti-L3T4 monoclonal antibody (MoAb) is administered al the time of antigen exposure. The process of tolerance induction may require the depletion of L3T4+ cells or it may be due to down-regulation or negative signaling of L3T4+ cells. We compared the effects of L3T4+ cell depletion and L3T4 antigen blockade at the time of primary antigen challenge on long-term humoral responses. Anti-L3T4 MoAb GK1·5 (IgG2b) and H129·19 (IgG2a) were used to deplete or block, respectively. L3T4+ cells. Following a short course of MoAb and antigen challenge with both aggregated human IgG (ag-HGG) and ovalbumin (OVA) in each mouse, primary response titres to each antigen in both MoAb treated groups were ∼1:102 compared with ∼1:105 in control mice. Repeated antigen challenge significantly increased the anti-OVA titre in both MoAb treated groups and by 150 days they were similar to controls. However, anti-HGG titres did not increase significantly in either of the MoAb treated groups. Thus either depletion of peripheral L3T4+ cells, or blockade of the L3T4 antigen without depletion of peripheral L3T4+ cells, can invoke a state of long-term antigen-specific tolerance to some antigens. Why the effect is restricted to particular antigens, and the exact mechanisms of tolerance induction remain to be determined.