Induction of Cell-Mediated Immunity to Chemically Modified Antigens in Guinea Pigs: II. The Interaction between Lipid-Conjugated Antigens, Macrophages, and T Lymphocytes

Protein antigens covalently conjugated with lipid groups (dodecanoic acid) have previously been shown to stimulate strong delayed-type hypersensitivity (DTH) without the aid of adjuvants. The present experiments show that lipid-conjugated bovine serum albumin (L-BSA) is taken up in vitro by macrophages (Mø) 25- to 50-fold more than unconjugated BSA or aminidated BSA, neither of which induces DTH. Macrophages that take up ¹²⁵I-labeled L-BSA in vitro stimulate DTH even more efficiently, when injected into syngeneic guinea pigs, than does soluble L-BSA. Tracer studies on the fate of radiolabeled BSA and L-BSA showed that much more L-BSA than BSA was retained by draining lymph nodes. Autoradiography demonstrated that ¹²⁵I-L-BSA is rapidly taken up by Mø in the medullary sinuses of the lymph nodes. Some of this antigen is then transported into the paracortex, a region in which T lymphocytes predominate. The capacity of lipophilic antigens to stimulate cell-mediated immune responses may be caused by their increased uptake by Mø, resulting in more efficient presentation to immunocompetent T lymphocytes. The anatomical site of this Mø-T cell interaction may be within the sinusoids or paracortex of the draining lymph nodes.