Contact sensitivity in the mouse: V. The role of macrophage cytophilic antibody in passive transfer and the effect of trypsin and anti-gamma globulin serum

Abstract

Contact-sensitivity skin reactions are produced in mice by percutaneous application of 2-phenyl-4-ethoxymethylene oxazolone (oxazolone) and can be detected by the increase in ear thickness after challenging the ears with oxazolone. A previous paper showed that these skin reactions can be transferred from immunized donors to irradiated recipients by peritoneal exudate cells and purified peritoneal exudate macrophages or lymphocytes. Immune lymphocytes were also able to convey a factor (presumably cytophilic antibody) to normal peritoneal exudate macrophages which enabled them to transfer skin reactions. This paper shows that skin reactions can be transferred by immune serum and by normal peritoneal exudate macrophages incubated with immune serum and then washed. In contrast lymphocytes incubated with immune serum and then washed were inactive. The working hypothesis was formed that passive transfer of skin reactions by macrophages from actively sensitized mice was due to cytophilic antibody while the reactions transferred by lymphocytes were due to an actively synthesized antibody. Experiment showed that treatment with trypsin abolished passive transfer by macrophages while transfer by lymphocytes was much less affected. Similarly rabbit anti-mouse gamma globulin serum abolished passive transfer by peritoneal macrophages but had no effect on transfer by lymphocytes. It was concluded that macrophages transferred skin reactions by virtue of an immunoglobulin receptor which they were unable to replace under the conditions of the experiment while lymphocytes behaved as though any surface immunoglobulin which they might possess was either unimportant or readily replaceable. These results do not mean that classical delayed hypersensitivity can be transferred by circulating antibodies or by macrophages incubated with immune serum. They suggest, however, that lymphocytes, macrophages coated with cytophilic antibody, and circulating antibody play a role in the skin reactions to oxazolone in the mouse. In most experiments the mice were irradiated the day before transfer. When the recipient mice were irradiated 5 days before transfer the 4-hr reaction transferred by the serum was unimpaired but the 24-hr reaction was abolished. This defect in inflammatory response was reversed by giving either bone marrow cells or purified peritoneal exudate cells 1 hr before the transfer of serum. In contrast, peritoneal lymphocytes were inactive. Irradiation also diminished nonspecific swelling caused by oxazolone. In this case, however, peritoneal macrophages did not reverse the defect although bone marrow cells were effective.