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.
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-Mphi). Our results show that: (1) mouse oil-induced peritoneal macrophages treated with HA produce in vitro significantly higher levels of interleukin (IL-1beta), tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and particularly IL-12 and express more B7-1 and B7-2 and ICAM-1 cell surface costimulatory molecules than Mphi treated with monomeric Ig (MM); (2) Mphi derivatized with TNP, treated or not with MM, induce in vivo antigen-specific unresponsiveness. In contrast TNP-Mphi 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-Mphi-HA. These results indicate that bypass of tolerance by treatment of TNP-Mphi 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-Mphi 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.
Ptak
W
W
Department of Immunology, College of Medicine, Jagiellonian University, Cracow, Poland.
Bryniarski
K
K
Nowak
B
B
Szczepanik
M
M
Ptak
M
M
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D006241:Haptens / Q000276:immunology; D006361:Heating; D007136:Immunoglobulins / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008808:Mice, Inbred CBA; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006241:Haptens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D018664:Interleukin-12