Effect of immunosuppressive agents on antigen retained in lymphoid follicles and collagenous tissue of immune mice

Abstract

We determined whether commonly used immunosuppressive agents affect the amount of antigen retained in lymphoid follicles and feet of immune mice. Mice immunized against human serum albumin (HSA) were injected in the hind footpads with 125I-HSA. Six days later antigen retained in the feet of immunized but nonimmunosuppressed animals was primarily present on the collagenous surface of the flexor and extensor tendons and was not cell associated. By contrast, antigen retained in the lymphoid follicles was located on the surface of dendritic cells. Similarly treated animals were given either cyclophosphamide (Cy), X irradiation, cortisone acetate (CA), or azathioprine (Az). The 125I-HSA persisting in spleen, popliteal lymph nodes (PLN), and hind feet was determined 1, 3, and 5 days after treatment. HSA retained in the spleen was depleted by Cy treatment whereas in PLN it was only minimally effected even though the total cell number was reduced by 90%. Autoradiography revealed that recognizable follicles were absent, but radiolabel remained localized to PLN superficial cortex. X irradiation (600 R) caused severe losses of HSA in spleen but only moderate losses in PLN. Lower doses (200 R) caused a significant depletion of lymphoid cells from spleen and PLN but did not affect retained antigen. Single or multiple doses of CA caused a large loss of HSA from spleen and PLN. Mice treated with Az demonstrated a loss of retained HSA from both spleen and PLN even though only minimal decreases in lymphoid cells occurred. Antigen retention in PLN was more resistant to immunosuppressants than antigen in the spleen. In contrast to these results in lymphoid organs where antigen is retained on dendritic cells, HSA retained in the acellular collagenous tissues of the hind foot did not decrease after treatment with any immunosuppressive agent.