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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
Author(s) -
Ptak,
Krzysztof Bryniarski,
Bernadeta Nowak,
Szczepanik
Publication year - 2000
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2000.00711.x
Subject(s) - immunogenicity , immune system , hapten , in vivo , antibody , antigen , immunology , tumor necrosis factor alpha , t cell , chemistry , biology , microbiology and biotechnology
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.