A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR

Deseke, Malte; Rampoldi, Francesca; Sandrock, Inga; Borst, Eva Maria; Böning, Heike; Ssebyatika, George; Jürgens, Carina; Plückebaum, Nina; Beck, Maleen; Hassan, Ahmed; Tan, Likai; Demera, Abdi; Janssen, Anika; Schmitz, Peter; Koenecke, Christian; Viejo‐Borbolla, Abel; Messerle, Martin; Krey, Thomas; Prinz, Immo

doi:10.1084/jem.20212525

Cited by 15 publications

(9 citation statements)

References 44 publications

(55 reference statements)

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“…3A–G ). It was recently demonstrated that γδ T cells can recognize HLA-DR in CMV-infected cells 26 , but the MCC26 cell line does not express HLA-DR, DP, or DQ (Supplementary Fig. 3H ).…”

Section: Resultsmentioning

confidence: 95%

Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Lien,

Ly,

Yang

et al. 2024

Nat Commun

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Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.

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Section: Resultsmentioning

confidence: 95%

Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Lien,

Ly,

Yang

et al. 2024

Nat Commun

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“…Over childhood, Vδ1 and Vδ2 cells exhibit increased clonal expansions, dissemination across sites, and functional maturation to cytolytic effectors—features consistent with antigen-driven differentiation. Clonal expansion of γδ T cells has been observed in response to infections in malaria ( 78 ) and CMV ( 79 ). This functional convergence of Vδ subsets and progression to a terminally differentiated state is accompanied by a loss of tissue γδ T cells in frequency (and density) ( 46 ) in mucosal sites in adults.…”

Section: Discussionmentioning

confidence: 99%

Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

Gray,

Caron,

Wells

et al. 2024

Sci. Immunol.

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During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.

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“…The early expansion and increase in HLA-DR expression of Vδ1 T cells could be the result of a general increase in activated immune cells, although HLA-DR increase was first noted in Vδ1 T cells among T cell subsets. Notably, CMV-induced adaptive Vδ1 T cells have been recently shown to recognize HLA-DR on activated immune cells, pointing to their role in inflammation-induced MHC-dependent immune response 48 .…”

Section: Discussionmentioning

confidence: 99%

The dynamics of γδ T cell responses in nonhuman primates during SARS-CoV-2 infection

et al. 2022

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Although most SARS-CoV-2 infections are mild, some patients develop systemic inflammation and progress to acute respiratory distress syndrome (ARDS). However, the cellular mechanisms underlying this spectrum of disease remain unclear. γδT cells are T lymphocyte subsets that have key roles in systemic and mucosal immune responses during infection and inflammation. Here we show that peripheral γδT cells are rapidly activated following aerosol or intra-tracheal/intra-nasal (IT/IN) SARS-CoV-2 infection in nonhuman primates. Our results demonstrate a rapid expansion of Vδ1 γδT cells at day1 that correlate significantly with lung viral loads during the first week of infection. Furthermore, increase in levels of CCR6 and Granzyme B expression in Vδ1 T cells during viral clearance imply a role in innate-like epithelial barrier-protective and cytotoxic functions. Importantly, the early activation and mobilization of circulating HLA-DR+CXCR3+ γδT cells along with significant correlations of Vδ1 T cells with IL-1Ra and SCF levels in bronchoalveolar lavage suggest a novel role for Vδ1 T cells in regulating lung inflammation during aerosol SARS-CoV-2 infection. A deeper understanding of the immunoregulatory functions of MHC-unrestricted Vδ1 T cells in lungs during early SARS-CoV-2 infection is particularly important in the wake of emerging new variants with increased transmissibility and immune evasion potential.

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A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR

Cited by 15 publications

References 44 publications

Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

The dynamics of γδ T cell responses in nonhuman primates during SARS-CoV-2 infection

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