Immune Response to Laminin,a Noncollagenous Glycoprotein of Basement Membrane,in a Syngeneic Murine System 1

Abstract

The immune response to the noncollagenous, attachment glycoprotein of basement membrane (laminin) was studied in a syngeneic murine system. Delayed-type hypersensitivity (DTH) was assayed in C57BL/6 mice by measuring footpad swelling following challenge with connective tissue antigens. Mice receiving a single sensitizing injection of laminin in Freund's complete adjuvant (FCA) developed a significant DTH response which peaked on Day 7, 24 hr after challenge with laminin or collagenase-treated laminin. Laminin-sensitized mice failed to show any significant footpad swelling when challenged with types I or IV collagen, or fibronectin throughout these experiments. Normal mice displayed no significant DTH when challenged with these collagenous or noncollagenous connective tissue antigens. Adoptive transfer of laminin-sensitized spleen cells into normal mice resulted in significant DTH responsiveness to challenge with laminin; depletion of T cells from the immune spleens abrogated this response. Twenty-four hours after challenge with laminin, histology of the footpad lesions of laminin-sensitized mice revealed a mononuclear cell infiltrate, characteristic of a DTH response. Mice receiving repeated injections of laminin in Freund's incomplete adjuvant (FIA) developed significant antibody responses as detected by the enzyme-linked immunosorbent assay (ELISA). Furthermore Pronase, but not collagenase, treatment of laminin destroyed its antigenicity. Laminin immune sera showed no reactivity when assayed on fibronectin or collagen types I-V. No cross-reactivity was exhibited by murine anti-type IV or anti-type I collagen antisera with laminin. These studies demonstrate the ability of isologous laminin to induce antigen-specific cell-mediated and humoral immunity in a murine model.