DR. ANDREA KNIGHT

Project: Investigations of human gamma-delta T cells: a new candidate for novel antiviral and antitumour immunotherapy

Person in Charge: prof. MUDr. Anna Vašků, CSc.

Host Institution: Department of Pathological Physiology, Faculty of Medicine, Masaryk University

Country of Origin: Czech Republic

Previous Place of Work: Great Britain

Project Duration: 36 months

Panel: Life Sciences

Abstract:

This project is focused on detailed characterization of antiviral and antitumour reactivity of gamma-delta (γδ) T cell populations both in healthy cytomegalovirus (CMV) seropositive donors and in patients with monoclonal gammopathy (MG) including multiple myeloma (MM), smouldering myeloma, monoclonal gammopathy of undetermined significance (MGUS). Human γδ T cells are effector lymphocytes of innate immunity involved in immune surveillance normally representing a minor population of circulating T cells. However the cells are largely expanded during CMV infection and also in MG patients.

I have published results demonstrating prominent anti-CMV reactivity of γδ T cells in patients following stem cell transplantation (Knight et al., 2010). I also showed long-term expansions of γδ T cells in patients during CMV reactivation suggesting their direct involvement in anti-CMV immune responses. My recent data (Knight et al., 2012) describing potent cytotoxicity of γδ T cells against myeloma plasma cells suggest that the innate immune responses become gradually deregulated as patients progress from MGUS to MM. The specific role of γδ T cells in this process remains unknown.

I plan to carry out: 1. Phenotypic analysis of γδ T cell populations in peripheral blood and matched bone marrow samples in MG patient cohorts and make comparison with healthy donors; 2. Functional analysis of γδ T cell anti-CMV and anti-myeloma reactivity (including cytotoxicity, proliferation, apoptosis and cytokine secretion); 3. Molecular analysis of gamma and delta chains of the TCR in expanded populations in healthy donors and MG patients; 4. The identification of the key interactions between the effector and target cells by selective antibody blocking or RNA interference knock-down of protein expression. The results of these studies will ultimately lead to a better understanding of anti-CMV and anti-myeloma reactivity of γδ T cells that could be explored in adoptive immunotherapy.