TY - JOUR
T1 - Phenotypic and functional characterization of pharmacologically expanded Vγ9Vδ2 T cells in pigtail macaques
AU - Barber-Axthelm, Isaac M.
AU - Wragg, Kathleen M.
AU - Esterbauer, Robyn
AU - Amarasena, Thakshila H.
AU - Barber-Axthelm, Valerie R.B.
AU - Wheatley, Adam K.
AU - Gibbon, Anne M.
AU - Kent, Stephen J.
AU - Juno, Jennifer A.
N1 - Funding Information:
The authors would like to acknowledge and thank the Melbourne Cytometry Platform for provision of flow cytometry services, and Vanta Jameson and Magdaline Sakkas from the Melbourne Brain Center Flow Cytometry Facility for provision of sorting services. All nonhuman primate studies were conducted at the Monash Animal Research Platform Gippsland Field Station. We acknowledge and thank Irwin Ryan, Graham Shillito, and staff for provision of animal care and sample collection support throughout the animal trials. The study was funded by the NHMRC through Program ( 1149990 ) and Investigator grants (A.K.W., GNT1173433 ; J.A.J., GNT2009308 ). I.M.B.A. is supported by a Melbourne Research Scholarship through the University of Melbourne .
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/3/17
Y1 - 2023/3/17
N2 - 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.
AB - 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.
KW - Biological sciences
KW - Components of the immune system
KW - Immunology
UR - https://www.scopus.com/pages/publications/85149903729
U2 - 10.1016/j.isci.2023.106269
DO - 10.1016/j.isci.2023.106269
M3 - Article
C2 - 36936791
AN - SCOPUS:85149903729
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 3
M1 - 106269
ER -
