Phenotypic and functional characterization of pharmacologically expanded Vγ9Vδ2 T cells in pigtail macaques

Authors:

• Barber-Axthelm, Isaac M.
• Wragg, Kathleen M.
• Esterbauer, Robyn
• Amarasena, Thakshila H.
• Barber-Axthelm, Valerie R.B.
• Wheatley, Adam K.
• Gibbon, Anne M.
• Kent, Stephen J.
• Juno, Jennifer A.

Details:

iScience, Volume 26, Issue 3, 2023-03-17

Article Link: Click here

While gaining interest as treatment for cancer and infectious disease, the clinical efficacy of Vγ9Vδ2 T cell-based immunotherapeutics has to date been limited. An improved understanding of γδ T cell heterogeneity across lymphoid and non-lymphoid tissues, before and after pharmacological expansion, is required. Here, we describe the phenotype and tissue distribution of Vγ9Vδ2 T cells at steady state and following in vivo pharmacological expansion in pigtail macaques. Intravenous phosphoantigen administration with subcutaneous rhIL-2 drove robust expansion of Vγ9Vδ2 T cells in blood and pulmonary mucosa, while expansion was confined to the pulmonary mucosa following intratracheal antigen administration. Peripheral blood Vγ9Vδ2 T cell expansion was polyclonal, and associated with a significant loss of CCR6 expression due to IL-2-mediated receptor downregulation. Overall, we show the tissue distribution and phenotype of in vivo pharmacologically expanded Vγ9Vδ2 T cells can be altered based on the antigen administration route, with implications for tissue trafficking and the clinical efficacy of Vγ9Vδ2 T cell immunotherapeutics.