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
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Monash Animal Research Platform, Monash University, Clayton, VIC 3800, Australia.
iScience. 2023 Feb 25;26(3):106269. doi: 10.1016/j.isci.2023.106269. eCollection 2023 Mar 17.
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 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 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.
虽然作为癌症和传染病的治疗方法受到关注，但迄今为止，基于Vγ9Vδ2 T细胞的免疫疗法的临床疗效有限。需要更好地了解在药理扩增前后，淋巴组织和非淋巴组织中γδ T细胞的异质性。在此，我们描述了猪尾猕猴在稳态下以及药理扩增后的Vγ9Vδ2 T细胞的表型和组织分布。静脉注射磷酸抗原并皮下注射重组人白细胞介素-2（rhIL-2）可促使血液和肺黏膜中的Vγ9Vδ2 T细胞强劲扩增，而气管内注射抗原后，扩增仅限于肺黏膜。外周血Vγ9Vδ2 T细胞的扩增是多克隆的，并且由于IL-2介导的受体下调，导致CCR6表达显著丧失。总体而言，我们表明，药理扩增的Vγ9Vδ2 T细胞的组织分布和表型可根据抗原给药途径而改变，这对组织转运和Vγ9Vδ2 T细胞免疫疗法的临床疗效具有影响。
