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- Title
Heat-Aggregated Immunoglobulins Increase In Vivo Immunogenicity of Mouse Hapten (TNP)-Derivatized Macrophages by Upregulation of Interleukin-12 Secretion and Expression of B7–1 and B7–2 Costimulatory Molecules.
- Authors
Ptak; Bryniarski; Nowak; Szczepanik
- Abstract
Antigen-antibody complexes (IC) can up or down regulate immune responses by induction of immunoregulatory cells. We have studied the effect of mouse heat-aggregated immunoglobulin (Ig) (HA) which have many biological activities similar to IC on immunogenicity of TNP-substituted macrophages (TNP-Mφ). Our results show that: (1) mouse oil-induced peritoneal macrophages treated with HA produce in vitro significantly higher levels of interleukin (IL-1β), tumor necrosis factor (TNF)-α, IL-6, IL-10 and particularly IL-12 and express more B7–1 and B7–2 and ICAM-1 cell surface costimulatory molecules than Mφ treated with monomeric Ig (MM); (2) Mφ derivatized with TNP, treated or not with MM, induce in vivo antigen-specific unresponsiveness. In contrast TNP-Mφ treated with HA induce significant contact sensitivity reaction even when injected into previously tolerized recipient animals. Treatment of recipients with anti-IL-12 Ab prevents immunization by TNP-Mφ-HA. These results indicate that bypass of tolerance by treatment of TNP-Mφ with HA is a result of an increased production of IL-12 by these cells and an enhanced expression of costimulatory molecules important in T cell–Mφ interactions. We suggest that a similar overcoming of tolerance through the action of IC may be responsible for the generation of autoantibodies of heterologous specificity in pathological conditions in which such complexes are formed.
- Subjects
IMMUNOGLOBULIN A; MACROPHAGES; LABORATORY mice
- Publication
Scandinavian Journal of Immunology, 2000, Vol 51, Issue 5
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1046/j.1365-3083.2000.00711.x