Natural killer cell-dependent immunoglobulin G2a anti-bovine serum albumin (BSA) response elicited by high molecular weight dextran-BSA conjugates associated with dextran-mediated macrophage-natural killer cell interaction.
The roles of the interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) produced during natural killer (NK) cell interaction with macrophages (M phi) were investigated as the basis for the induction of immunoglobulin G2a (IgG2a) anti-bovine serum albumin (BSA) responses by high molecular weight dextran conjugated to BSA (HMW-DEX-BSA). BALB/c mice immunized with HMW-DEX-BSA produced significantly higher levels of both IgG1 and IgG2a anti-BSA than did mice immunized with BSA alone. Both IgG1 and IgG2a anti-BSA levels were higher in mice immunized with BSA conjugated to dextran of molecular weight (MW) 5 000 000-40 000 000 compared with dextran of MW 10,000-60,000. The enhancement of anti-BSA IgG2a levels but not of anti-BSA IgG1 levels was inhibited when free BSA was added to the HMW-DEX-BSA conjugate. NK cell depletion during HMW-DEX-BSA immunization of mice resulted in significantly lower anti-BSA IgG2a levels without affecting anti-BSA IgG1 levels. Naive splenocytes or M phi + NK cell co-cultures incubated with HMW-DEX or HMW-DEX-BSA produced higher IFN-gamma levels than splenocytes or co-cultures incubated with BSA alone. HMW-DEX stimulated both IFN-gamma and IL-12 production by M phi + NK cell co-cultures in a dose-dependent manner. DEX-induced IFN-gamma production by NK cells was dependent upon the presence of IL-12, and IL-12 production by M phi was dependent upon the presence of IFN-gamma in these co-cultures. Both M phi and NK cells bound DEX to their surfaces. These data demonstrate that BSA linked to HMW-DEX enhanced both T-helper-1- and T-helper-2-associated antibody responses to BSA. The results also indicate an IL-12-dependent positive feedback interaction between NK cells and M phi that supports a NK cell/IFN-gamma-dependent mechanism for enhancement of anti-BSA IgG2a antibody responses in mice immunized with HMW-DEX-BSA protein conjugates.
Ediriwickrema
C P
CP
Department of Microbiology, Pathology and Parasitology, North Carolina State University, Raleigh, NC 27606, USA.
Tonkonogy
S L
SL
Hammerberg
B
B
D000276:Adjuvants, Immunologic; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D003911:Dextrans / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D012710:Serum Albumin, Bovine / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000276:Adjuvants, Immunologic; D003911:Dextrans; D007074:Immunoglobulin G; D018664:Interleukin-12; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma