We determined whether (1) long term antigen retention is present in distal sites after footpad challenge of immune mice; (2) if antigen retained in the foot is selectively localized; and (3) if the foot is adversely affected by the retained antigen. Mice immune or non-immune to human serum albumin (HSA) were injected in the hind footpads with 125I-HSA. In immune mice rapid clearance of radiolabel occurred in the liver, lungs, kidney, blood and urine but radiolabel was retained in the hind feet, draining lymph nodes and spleen. Non-immune mice rapidly cleared radiolabel from these sites. Autoradiography revealed that most of the radiolabel in the feet was in flexor tendons and tendon sheaths. Electron microscope autoradiography indicated that antigen was associated with collagen at the tendon surface, but not with cells or cell processes. Radiolabel solubilized from the feet, lymph nodes and spleen could be specifically precipitated with rabbit anti-HSA. Histological examination of the tendon and surrounding tissues did not show that retained antigen was causing inflammation or chronic tissue damage. Nanogram levels of antigen could elicit swelling in the sensitized foot even if the antigen was injected at a remote site, but mice immunized by other routes or against other antigens did not show footpad swelling. Antigen retained on collagenous tissues may induce hypersensitivity and thus play a role in rheumatic diseases.
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