Heterogenous Populations of Tissue-Resident CD8<sup>+</sup> T Cells Are Generated in Response to Infection and Malignancy.
Abstract
Tissue-resident memory CD8<sup>+</sup> T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8<sup>+</sup> T cells, including a Blimp1<sup>hi</sup>Id3<sup>lo</sup> tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections and a molecularly distinct Blimp1<sup>lo</sup>Id3<sup>hi</sup> tissue-resident memory population that subsequently accumulated at later infection time points. These Trm populations exhibited distinct cytokine production, secondary memory potential, and transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8<sup>+</sup> T cell populations with tissue-resident gene-expression signatures that shared features of terminally exhausted and progenitor-exhausted T cells, respectively. Our findings provide insight into the development and functional heterogeneity of Trm cells, which has implications for enhancing vaccination and immunotherapy approaches.
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Linked Datasets (5)
Single Cell RNA-Seq of CD8+ T cell subsets responding to tumor
Mus musculus16 data files
| File | Type | Size |
|---|---|---|
| TIL-Try3Spleen1_S10_L005_R1_001.fastq.gz | RNA-Seq | 906.5 MB |
| TIL-Try3Spleen1_S11_L005_R1_001.fastq.gz | RNA-Seq | 382.3 MB |
| TIL-Try3Spleen1_S12_L005_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| TIL-Try3Spleen1_S9_L005_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| TIL-Try3Spleen2_S13_L005_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| TIL-Try3Spleen2_S14_L005_R1_001.fastq.gz | RNA-Seq | 901.4 MB |
| TIL-Try3Spleen2_S15_L005_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| TIL-Try3Spleen2_S16_L005_R1_001.fastq.gz | RNA-Seq | 843.8 MB |
| TIL-Try3TIL1_S1_L005_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| TIL-Try3TIL1_S2_L005_R1_001.fastq.gz | RNA-Seq | 836.4 MB |
| TIL-Try3TIL1_S3_L005_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| TIL-Try3TIL1_S4_L005_R1_001.fastq.gz | RNA-Seq | 970.7 MB |
| TIL-Try3TIL2_S5_L005_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| TIL-Try3TIL2_S6_L005_R1_001.fastq.gz | RNA-Seq | 1.6 GB |
| TIL-Try3TIL2_S7_L005_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| TIL-Try3TIL2_S8_L005_R1_001.fastq.gz | RNA-Seq | 875.6 MB |
RNA-Seq of CD8+ T cell subsets during LCMV infection II
Mus musculus8 data files
| File | Type | Size |
|---|---|---|
| 000008565169_A10.R1.fastq.gz | RNA-Seq | 248.3 MB |
| 000008565169_B10.R1.fastq.gz | RNA-Seq | 251.0 MB |
| 000008565169_C10.R1.fastq.gz | RNA-Seq | 192.7 MB |
| 000008565169_D10.R1.fastq.gz | RNA-Seq | 236.6 MB |
| 000008565169_G09.R1.fastq.gz | RNA-Seq | 270.7 MB |
| 000008565169_G10.R1.fastq.gz | RNA-Seq | 230.5 MB |
| 000008565169_H09.R1.fastq.gz | RNA-Seq | 234.0 MB |
| 000008565169_H10.R1.fastq.gz | RNA-Seq | 225.8 MB |
Heterogeneity of tissue-resident CD8+ T cells in response to infection and malignancy
Mus musculusRNA-Seq of CD8+ T cell subsets in B16-GP33 tumor
Mus musculus12 data files
| File | Type | Size |
|---|---|---|
| SK-3L4G_G10.R1.fastq.gz | RNA-Seq | 360.6 MB |
| SK-3L4G_G11.R1.fastq.gz | RNA-Seq | 276.8 MB |
| SK-3L4G_G12.R1.fastq.gz | RNA-Seq | 308.3 MB |
| SK-3L4G_G2.R1.fastq.gz | RNA-Seq | 311.4 MB |
| SK-3L4G_G3.R1.fastq.gz | RNA-Seq | 300.8 MB |
| SK-3L4G_G4.R1.fastq.gz | RNA-Seq | 320.5 MB |
| SK-3L4G_G5.R1.fastq.gz | RNA-Seq | 320.0 MB |
| SK-3L4G_G6.R1.fastq.gz | RNA-Seq | 323.3 MB |
| SK-3L4G_G7.R1.fastq.gz | RNA-Seq | 337.8 MB |
| SK-3L4G_G8.R1.fastq.gz | RNA-Seq | 272.0 MB |
| SK-3L4G_G9.R1.fastq.gz | RNA-Seq | 293.4 MB |
| SK-3L4G_H1.R1.fastq.gz | RNA-Seq | 376.4 MB |
RNA-Seq of CD8+ T cell subsets during LCMV infection I
Mus musculus27 data files
| File | Type | Size |
|---|---|---|
| 000008565169_E11.R1.fastq.gz | RNA-Seq | 239.0 MB |
| 000008565169_F11.R1.fastq.gz | RNA-Seq | 236.9 MB |
| 000008565169_G11.R1.fastq.gz | RNA-Seq | 157.0 MB |
| 000008565169_H11.R1.fastq.gz | RNA-Seq | 168.0 MB |
| 000008570169_A01.R1.fastq.gz | RNA-Seq | 145.7 MB |
| 000008570169_A02.R1.fastq.gz | RNA-Seq | 179.7 MB |
| 000008570169_A03.R1.fastq.gz | RNA-Seq | 197.5 MB |
| 000008570169_A04.R1.fastq.gz | RNA-Seq | 211.8 MB |
| 000008570169_B01.R1.fastq.gz | RNA-Seq | 229.8 MB |
| 000008570169_B02.R1.fastq.gz | RNA-Seq | 191.3 MB |
| 000008570169_B03.R1.fastq.gz | RNA-Seq | 234.2 MB |
| 000008570169_B04.R1.fastq.gz | RNA-Seq | 185.5 MB |
| 000008570169_C02.R1.fastq.gz | RNA-Seq | 212.0 MB |
| 000008570169_C04.R1.fastq.gz | RNA-Seq | 192.9 MB |
| 000008570169_D02.R1.fastq.gz | RNA-Seq | 206.6 MB |
| 000008570169_D04.R1.fastq.gz | RNA-Seq | 163.2 MB |
| 000008570169_E01.R1.fastq.gz | RNA-Seq | 308.4 MB |
| 000008570169_E02.R1.fastq.gz | RNA-Seq | 205.6 MB |
| 000008570169_E03.R1.fastq.gz | RNA-Seq | 247.3 MB |
| 000008570169_F01.R1.fastq.gz | RNA-Seq | 310.3 MB |
| 000008570169_F02.R1.fastq.gz | RNA-Seq | 240.1 MB |
| 000008570169_F03.R1.fastq.gz | RNA-Seq | 271.7 MB |
| 000008570169_G02.R1.fastq.gz | RNA-Seq | 244.2 MB |
| 000008570169_G03.R1.fastq.gz | RNA-Seq | 301.5 MB |
| 000008570169_H01.R1.fastq.gz | RNA-Seq | 181.4 MB |
| 000008570169_H02.R1.fastq.gz | RNA-Seq | 200.3 MB |
| 000008570169_H03.R1.fastq.gz | RNA-Seq | 211.1 MB |
Potentially Related Datasets (4)
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
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