Immune retention: immunological requirements for maintaining an easily degradable antigen in vivo

Radioactive human serum albumin (125I-HSA) was injected into the hind foot pads of unimmunized mice, actively immunized mice and mice passively immunized with mouse or rabbit anti-HSA serum. Eleven days later the unimmunized mice had cleared most of the 125I-HSA. In contrast, a high concentration of 125I-HSA was retained in the feet and draining lymph nodes and, to a lesser extent, in the spleen of the actively or passively immunized mice. Although immune retention required specific antibody, it appeared to be independent of T-cells or T-cell factors, since passively immunized nude mice retained antigen as well as actively or passively immunized normal mice. Depletion of the complement system with cobra venom factor (CVF) increased antigen retention in the feet but decreased retention in the spleen. Treatment with CVF did not decrease antigen retention in lymph nodes of actively immunized mice. Such treatment did, however, decrease retention in lymph nodes of passively immunized mice although not to the same extent as in the spleen. Retention of antigen in the feet was not only complement-independent but was also Fc independent, since F(ab')2 fragments of IgG could mediate immune retention. Antigen dose response studies indicated that immune retention in lymph nodes occurred optimally with minute amounts of antigen, whereas optimal retention in the feet required much higher concentrations of antigen. Foot pad injections of non-radiolabelled HSA eliminated 60% of the radioactivity retained in the foot pads of immunized mice. In contrast, non-radioactive egg albumin (EA) had almost no effect on retained HSA. However, if the mice were immunized to both EA and HSA, an injection of EA would displace a significant amount of retained HSA. Complexes of one specificity can apparently displace some retained antigen of a differing specificity.