Strategies for the Stimulation of Th Cell Subsets

Golding, Hana; Zaitseva, Marina; Lapham, Cheryl; Golding, Basil

doi:10.1007/978-1-4613-0357-2_7

Cited by 1 publication

(1 citation statement)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B. abortus was shown to promote a TC1 or TH1 type of differentiation in both human and murine systems (13,14,36). To determine whether chemokine production in response to HBa occurs in polarized TC1 or TC2 CD8 ϩ T cells (or in both), human T cells were cultured in vitro with HBa for 2 days and then subjected to three-color flow cytometry to analyze the levels of intracellular MIP-1␣ or MIP-1␤ in CD8 ϩ T cells producing either IFN-␥ or IL-4 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Human Peripheral Blood T Cells, Monocytes, and Macrophages Secrete Macrophage Inflammatory Proteins 1α and 1β following Stimulation with Heat-InactivatedBrucella abortus

et al. 2001

View full text Add to dashboard Cite

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-␥) in both CD4؉ and CD8 ؉ T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit ␤-chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted ␤-chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-␥ neutralizing antibodies. Among purified T cells, macrophage inflammatory protein 1␣ and 1␤ (MIP-1␣ and MIP-1␤, respectively) secretion was observed primarily in human CD8؉ T cells. The kinetics of ␤-chemokine induction in T cells were slow (3 to 4 days). The majority of ␤-chemokine-producing CD8 ؉ T cells also produced IFN-␥ following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8 ؉ T cells contained stored MIP-1␤ that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-1␣ and MIP-1␤ production in elutriated monocytes and even higher levels in macrophages. In these cells, ␤-chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte-and macrophage-derived ␤-chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.The discovery that several ␤-chemokines (i.e., macrophage inflammatory proteins 1␣ and 1␤ [MIP-1␣ and MIP-1␤, respectively] and RANTES) secreted by short-term human CD8 ϩ cell lines can effectively block infection of human peripheral blood mononuclear cells (PBMCs) with macrophage-

show abstract

Section: Resultsmentioning

confidence: 99%