Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1 alpha and 1 beta following stimulation with heat-inactivated Brucella abortus

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for thera peutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD 4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ab ility of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit bet a -chemokines, known to bind to the human immunodeficiency virus type 1 (HI V-1) coreceptor CCRS and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta -chemokines following sti mulation with HBa, and this effect could not be blocked by anti-IFN-gamma n eutralizing antibodies. Among purified T cells, macrophage inflammatory pro tein lo and Ip (MIP-1 alpha and MIP-1 beta, respectively) secretion was obs erved primarily in human CD8(+) T cells. The kinetics of beta -chemokine in duction in T cells were slow (3 to 4 days). The majority of beta -chemokine -producing CD8(+) T cells also produced IFN-gamma following HBa stimulation , as determined by triple-color intracellular staining. A significant numbe r of CD8(+) T cells contained stored MIP-1 beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-la and MIP- IP production in elutriated monocytes and even higher levels in macrophages . In these cells, beta -chemokine mRNA was upregulated within 30 min and pr oteins were secreted within 4 h of stimulation. The monocyte- and macrophag e-derived beta -chemokines were sufficient to block CCR5-dependent HIV-1 en velope-mediated cell fusion. These data suggest that, in addition to the ab ility of HBa to elicit antigen-specific humoral and cellular immune respons es, HBa-conjugated HIV-1 proteins or peptides would also generate innate ch emokines with antiviral activity that could limit local viral spread during vaccination in vivo.