Brucella abortus regulates bovine macrophage-T-cell interaction by major histocompatibility complex class II and interleukin-1 expression

Abstract

T-cell activation is dependent on nominal antigen associated with major histocompatibility complex (MHC) class II molecules and interleukin-l (IL-1), both provided by antigen-presenting cells. We have studied the effects of Brucella abortus and recombinant bovine gamma interferon (IFN-y) on bovine macrophage expression of MHC class HI and IL-1 molecules and subsequent T-cell proliferation in response to B. abortus.When peripheral blood mononuclear cells were cocultured with B. abortus and IFN-y, increasing amounts of IFN-y, from l to 100 U/ml, down regulated T-cell proliferation. Expression of MHC class II molecules on macrophages was incr'eased independently by IFN-y or B. abortus treatment. Thus, class II molecule expression was not the cause of down regulation of T-cell proliferation as observed in other systems. However, B. abortus-IFN-y-treated 'macrophages obtained from overnight cultures had minimal membrane IL-1 compared with macrophages treated 'with B. abortus alone. Loss of membrane IL-1 required IFN--y and the o-polysaccharide of the lipopolysaccharide. IFN-,y at 1 U/ml in combination with B. abortus produced a 32% decrease in T-cell response, while IFN-y at 100 U/ml added to B. abortus-treated cultures produced an 82% reduction in T-cell response. Membrane IL-1 levels were not altered when recombinant bovine IFN-a or the rough strain 45/20 of B. abortus, which lacks the o-polysaccharide, was used. Secreted IL-1 levels were unaffected by IFN-y and B. abortus treatment. The addition of recombinant bovine IL-1 (0.001 to 0.1 ng/ml) to B. abortus-and IFN--y-treated cultures failed to provide a signal necessary for T-cell proliferation. These data suggest that membrane IL-1 has a key role in T-cell activation in response to B. abortus. When the o-polysaccharide of B. abortus lipopolysaccharide is combined with IFN--y at an inappropriate time during an immune response, T-cell proliferation is prevented and cannot be restored by the addition of exogenous IL-1.

Isolation of Brucella abortus ssb and uvrA genes from a genomic library by use of lymphocytes as probes

“…B. abortus S19 was kindly provided by Barb Martin, Veterinary Services, National Animal Disease Center, Ames, Iowa. The bacilli were killed by gamma irradiation (137Cs) and added to the adherent cells, and the culture was incubated overnight at 37°C as described elsewhere (32).…”

Alteration of protective and serologic responses in BALB/c mice vaccinated with chemically modified versus nonmodified proteins of Brucella abortus 19

“…Because immunity in brucellosis is due to both cell-mediated and humoral effects, both B-and T-cell responders must be considered when subunit vaccines are used (2,7,27,34). Because of this, an important question in the development of subunit vaccines is whether the different components can be manipulated to give specific epitopic responses.…”

“…Because of this, an important question in the development of subunit vaccines is whether the different components can be manipulated to give specific epitopic responses. Some investigators (1,15,18,22,(32)(33)(34) suggest that chemical modifications of nonimmunogenic or poorly immunogenic substances can convert them to highly effective immunogens, while others (9,(22)(23)(24) reported that immunization with chemically modified antigens favors cell-mediated responses whereas unmodified antigens tend to elicit humoral responses. In our laboratory, unmodified protein antigens were not highly effective against infection by B. abortus although they usually induced excellent humoral antibody responses (28-30, 39, 40).…”

Characterization and immunogenicity of the heat shock protein, hsp60 of Brucella abortus

“…This inhibition has been partially accounted for in neutrophils, where the ingested brucellae apparently secrete adenine, and 5'-guanosine monophosphate, which inhibit degranulation of primary granules, resulting in decreased myeloperoxidase dependent oxidative attack [79][80][81]. Brucella LPS has been shown to decrease the surface-bound expression of IL-1 on macrophages in the presence of IFN-y, leading to a decreased ability to stimulate proliferation of T cells [85,86].…”