Mechanistic investigations of a TLR4 adjuvant effects on γ₉δ₂ T cells.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B529
Abstract ID: 5918

Presenting Author:
Kathleen Phelps , Graduate Student at Saint Louis Univ. Sch. of Med.

Abstract:

γδ T cells are ideal effector cells against cancer and pathogens for numerous reasons: they are found in blood, mucosa, and lymphoid organs, develop memory responses independent of MHC restriction, present antigen, produce cytokines, and are cytolytic. An obstacle for the development of biomedical interventions targeting γδ T cells is the need for an adjuvant that promotes their expansion and is suitable for human use. The adjuvant routinely used, IL-2, has multiple drawbacks limiting its use for vaccination. Our lab has shown that BCG vaccination induces memory γ₉δ₂ T cells. Those γ₉δ₂ T cells are expanded in vitro by M. tuberculosis, M.bovis (BCG), and our lab’s vaccine candidate 6-O-methylglucoselipopolysaccharide (mGLP), with IL-2, and subsequently inhibit intracellular mycobacterial growth.

We recently demonstrated that the synthetic TLR4 adjuvant, Glucopyranosyl Lipid A (GLA), promotes expansion of mGLP specific γδ T cells. In vitro expansion assays were performed using human peripheral blood mononuclear cells, dendritic cells, antigen, and adjuvant. The absolute numbers of expanded effector γδ T cells were calculated using flow cytometry after 7 days of culture. We report that the ability of GLA to promote γδ T cell expansion is dependent upon TLR4. The ability of this adjuvant to promote γδ T cell responses has broad implications for vaccine design and improved understanding of the role of γδ T cells for protection against infectious agents and cancer.