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Updated: Aug 8, 2026
Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Single-cell immunophenotyping identifies CD8+GZMK+IFNG+ T cells as a key immune population in cutaneous Lyme disease
Edel Aron1, Hailong Meng2, Alexia A Belperron3
1Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA.
Insights
Researchers identified specific T cells in Lyme disease skin lesions that may help fight Borrelia burgdorferi (Bb) infection. These inflammatory T cells, alongside other skin cells, are key to the body's early defense against this tick-borne illness.
Area of Science:
- Immunology
- Microbiology
- Dermatology
Background:
- Erythema migrans (EM) is the primary skin manifestation of Lyme disease, caused by Borrelia burgdorferi (Bb).
- Previous research utilized scRNA-Seq to analyze B cell responses within EM lesions.
Purpose of the Study:
- To comprehensively profile T cell responses in EM lesions compared to healthy skin using an expanded sample size.
- To identify specific T cell subsets and their functions in the cutaneous immune response to Bb infection.
Main Methods:
- Single-cell RNA sequencing (scRNA-Seq) combined with adaptive immune receptor sequencing (AIRR-seq).
- Comparative analysis of immune cell populations in erythema migrans lesions versus uninvolved skin.
Main Results:
- Identification of clonally expanded CD8+GZMK+IFNG+ T cells with high or intermediate IFNG expression in EM lesions.
- These CD8+ T cells showed differential expression of IFN-regulated genes and potential inflammatory functions.
- Endothelial cells, fibroblasts, and pericytes were identified as major producers of T cell-recruiting chemokines.
Conclusions:
- The study provides a detailed understanding of the cutaneous T cell response to Bb infection.
- Specific T cell subsets, particularly CD8+GZMK+IFNG+ T cells, may play a crucial role in the early inflammatory defense against Lyme disease.
- Non-immune cells in the skin actively contribute to orchestrating the immune response by recruiting T cells.
Abstract:
The skin lesion erythema migrans (EM) is the first clinical sign of Lyme disease, an infection due to the tick-transmitted bacterium Borrelia burgdorferi (Bb). Previously, we used scRNA-Seq to characterize the cutaneous immune response in the EM lesion, focusing on B cells. Here, with an expanded sample size, we profiled T cell responses in EM lesions compared to autologous uninvolved skin. In addition to CD4+ T cell subsets known to be abundant in the EM lesion, we identified clonally expanded CD8+GZMK+IFNG+ T cells that comprised cells with high or intermediate IFNG expression. These cells exhibited significant differential expression of IFN-regulated genes and included subsets with low cytotoxic gene expression, suggesting an inflammatory potential that may contribute to early defense against Bb within the EM lesion. In addition, we found that endothelial cells, fibroblasts, and pericytes were the main producers of key T cell-recruiting chemokines. These studies using single-cell transcriptomics with adaptive immune receptor sequencing provide a comprehensive interrogation of the cutaneous T cell response to Bb infection and insight into the orchestration of the skin barrier defense to this vector-borne pathogen.
