<i>γδ</i> T Cells and dendritic cells in refractory Lyme arthritis

Divan, Ali; Budd, Ralph C.; Tobin, Richard P.; Newell‐Rogers, M. Karen

doi:10.1189/jlb.2ru0714-343rr

Cited by 11 publications

(4 citation statements)

References 134 publications

(186 reference statements)

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“…About 0.5% of γδ T cells in mice can directly bind to the inducible non-classical MHC Ib molecule T10 and the related T22, which lack an antigen-binding groove (Crowley et al, 2000). Recognition of lipid antigens in CD1 has also been observed (Divan et al, 2015). However, they can also bind directly to protein antigens (phycoerythrin) as well as haptens (Zeng et al, 2012;Chien et al, 2014;D'Souza et al, 2019).…”

Section: T Cell Responsesmentioning

confidence: 99%

Section: Responses To B Burgdorferi By Nonconventional T Cellsmentioning

confidence: 99%

“…T cells expressing the γδ TCR develop from the thymus throughout life, although their development includes early developmental waves that seed various tissues, including the skin, where they may interact with B. burgdorferi shortly after its release from the tick into the mammalian host (Divan et al, 2015). The main focus of studies on γδ T cells in infection has been on lymph tissue of mice and synovial fluid of patients with Lyme arthritis (Divan et al, 2015). Collectively, the results suggest that γδ T cells respond to cell stress and inflammatory responses triggered indirectly through TLR activation, as well as release of pro-inflammatory cytokines, such as IL-1β, that occurs during arthritis development.…”

Section: Responses To B Burgdorferi By Nonconventional T Cellsmentioning

confidence: 99%

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Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Wooten¹,

Baumgarth²

2022

Current Issues in Molecular Biology

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The mammalian host responds to infection with Borrelia spirochetes through a highly orchestrated immune defense involving innate and adaptive effector functions aimed toward limiting pathogen burdens, minimizing tissue injury, and preventing subsequent reinfection. The evolutionary adaptation of Borrelia spirochetes to their reservoir mammalian hosts may allow for its persistence despite this immune defense. This review summarizes our current understanding of the host immune response to B. burgdorferi sensu lato, the most widely studied Borrelia spp. and etiologic agent of Lyme borreliosis. Pertinent literature will be reviewed with emphasis on in vitro, ex vivo and animal studies that influenced our understanding of both the earliest responses to B. burgdorferi as it enters the mammalian host and those that evolve as spirochetes disseminate and establish infection in multiple tissues. Our focus is on the immune response of inbred mice, the most commonly studied animal model of B. burgdorferi infection and surrogate for one of this pathogen's principle natural reservoir hosts, the white-footed deer mouse. Comparison will be made to the immune responses of humans with Lyme borreliosis. Our goal is to provide an understanding of the dynamics of the mammalian immune response during infection with B. burgdorferi and its relation to the outcomes in reservoir (mouse) and non-reservoir (human) hosts.Curr. Issues . caister.com/cimb caister.com/cimb 145 Curr. Issues Mol. Biol. Vol. 42 Immune Response to Borrelia Bockenstedt et al.

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Section: T Cell Responsesmentioning

confidence: 99%

Section: Responses To B Burgdorferi By Nonconventional T Cellsmentioning

confidence: 99%

Section: Responses To B Burgdorferi By Nonconventional T Cellsmentioning

confidence: 99%

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Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Wooten¹,

Baumgarth²

2022

Current Issues in Molecular Biology

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“…In patients with post-antibiotic LA, 5% of CD3+ T cells in SFMC samples obtained near the time of IV antibiotic treatment were γδ T cells, a significantly higher percentage than that in patients with antibiotic-responsive LA or RA. In a seminal study, Budd et al reported marked expansion of γδ T cells in SFMC samples (11-31% of T cells at that site) among 7 patients with refractory LA (33,34). During early disseminated infection, γδ T cells may have a cytotoxic role in controlling spirochetal spread by trapping organisms in obliterative vascular lesions (12).…”

Section: Discussionmentioning

confidence: 99%

Cell‐Mediated Cytotoxicity in Lyme Arthritis

Ordóñez

Lochhead

Strle

et al. 2023

Arthritis & Rheumatology

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Objective Obliterative microvascular lesions are found in the synovial tissue of ~50% of patients with post‐antibiotic Lyme arthritis (LA) and correlate with autoantibodies to certain vascular antigens. In this study, we identified lymphocytes with cytotoxic potential that may also mediate this feature of synovial pathology. Methods The cytotoxic potential of lymphocytes and their T cell receptor (TCR) Vβ gene usage were determined using samples of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with antibiotic‐responsive or post‐antibiotic LA. Cell phenotypes were analyzed using flow cytometry and intracellular cytokine staining. Immunohistochemistry was performed on post‐antibiotic synovial tissue samples. Results In SFMC and PBMC samples, the percentages of CD8+ T cells and double‐negative T cells (primarily γδ T cells) were greater among 22 patients with post‐antibiotic LA than in 14 patients with antibiotic‐responsive LA. Moreover, CD8+ T cells and γδ T cells often expressed cytotoxic mediators, granzyme A/granzyme B, and perforin. The same 3 TCR Vβ segments were over‐represented in both CD4+ T cells and CD8+ T cells in SFMC samples from post‐antibiotic LA patients. In synovial tissue samples from 3 patients with post‐antibiotic LA, CD8+ T cells intermixed with CD4+ T cells were seen around blood vessels, and 2 patients with microvascular damage had autoantibodies to vascular‐associated antigens. One of these 2 patients, the one in whom cytotoxicity appeared to be active, had complement (C5b–9) deposition on obliterated vessels. Very few natural killer cells or γδ T cells were seen. Conclusion We propose that CD8+ T cell–mediated cytotoxicity, CD4+ T cell help, autoantibodies to vascular antigens, and complement deposition may each have a role in microvasculature damage in post‐antibiotic LA.

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Pathogenesis and Immune Defense

Brissette

Kraiczy

2022

Lyme Borreliosis

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γδ T Cells and dendritic cells in refractory Lyme arthritis

Cited by 11 publications

References 134 publications

Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Cell‐Mediated Cytotoxicity in Lyme Arthritis

Pathogenesis and Immune Defense

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