T-cells

A T-cell, or T lymphocyte, is a type of white blood cell that plays a central role in cell-mediated immunity. They mature in the thymus and can be distinguished from other lymphocytes, by the presence of a T-cell receptor on the cell surface. There are several subsets of T-cells, such as cytotoxic T-cells, regulatory T-cells, helper T-cells and natural killer T-cells, with functions related to both innate and adaptive immunity.

In the Blood Atlas we have 609 cell lineage enriched genes and 103 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 741 genes are cell lineage group enriched and an additional 45 genes are enhanced in this cell lineage. Altogether, 1395 genes are elevated and among these 270 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Figure 1. The distribution of all genes across the five specificity categories based on transcript abundance in T-cell lineage as well as in the other 5 cell lineages.

Table 1. Number of genes in the subdivided categories of elevated expression in T-cell lineage

Distribution in the six cell lineages
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Lineage enriched 475012410 609
Group enriched 0068952 741
Lineage enhanced 44010 45
Total 519081462 1395

Table 2. The genes with the highest level of enriched expression in T-cell lineage. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of T-cell lineage expression to the second highest cell lineage.

Gene Description Cell lineage distribution pTPM Specificity score
FANK1 fibronectin type III and ankyrin repeat domains 1 Detected in single 69.1 284
FOXP3 forkhead box P3 Detected in single 57.5 260
CTLA4 cytotoxic T-lymphocyte associated protein 4 Detected in single 52.6 248
ELOVL4 ELOVL fatty acid elongase 4 Detected in single 31.1 191
PRSS35 serine protease 35 Detected in single 25.1 172
NEFL neurofilament light Detected in single 15.3 138
CD248 CD248 molecule Detected in single 25.7 122
REG4 regenerating family member 4 Detected in single 26.9 115
CPA5 carboxypeptidase A5 Detected in single 67.6 114
EDAR ectodysplasin A receptor Detected in single 8.4 102
ADAM12 ADAM metallopeptidase domain 12 Detected in single 8.2 98
MXRA8 matrix remodeling associated 8 Detected in single 7.8 98

T-regs

Regulatory T-cells (T-regs) has an important role in maintaining immunological tolerance, by suppressing autoreactive T-cells that have escaped negative regulation and by being involved in ending a T-cell mediated immune reaction.

In the Blood Atlas we have 67 T-reg enriched genes and 19 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 163 genes are cell type group enriched and an additional 212 genes are enhanced in this cell type. Altogether, 442 genes are elevated and among these 134 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The T-regs were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. The T-reg population was sorted as CD3+/CD4+/CD127low/CD25+/CCR4+ sub-population of lymphocytes (FSClow/SSClow). 4,000 – 7,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 51 % (n= 9984) of all human proteins (n=19,670) are expressed in the T-regs and 163 of these genes show an elevated expression in T-regs compared to the other 17 cell types (see figure below).

Figure 2. The distribution of all genes across the five specificity categories based on transcript abundance in T-reg cells as well as in the other 17 cell types.

Table 3. Number of genes in the subdivided categories of elevated expression in T-reg cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 392170 67
Group enriched 0521092 163
Cell type enhanced 3998741 212
Total 781711903 442

Table 4. The genes with the highest level of enriched expression in T-reg cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of T-reg cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
BTBD16 BTB domain containing 16 Detected in single 0.7 29
KRT24 keratin 24 Detected in single 0.5 24
SPACA5B sperm acrosome associated 5B Detected in single 0.3 19
BDKRB1 bradykinin receptor B1 Detected in single 0.2 19
RPRM reprimo, TP53 dependent G2 arrest mediator homolog Detected in single 0.3 19
BTG4 BTG anti-proliferation factor 4 Detected in single 0.2 18
PCDHB4 protocadherin beta 4 Detected in single 0.2 17
FANK1 fibronectin type III and ankyrin repeat domains 1 Detected in some 69.1 14
SEMA3G semaphorin 3G Detected in single 1.8 14
KRTAP7-1 keratin associated protein 7-1 (gene/pseudogene) Detected in single 0.4 13
OR13C8 olfactory receptor family 13 subfamily C member 8 Detected in single 0.1 13
BMP10 bone morphogenetic protein 10 Detected in single 0.1 12

gdTCRs

Gamma delta T cells (gdTCR cells) are a small subset of T cells with a gamma delta T-cell receptor (TCR), instead of the common alpha beta TCR, on the cell surface. gdTCR cells seem to be able to recognize whole proteins and not only peptides on the surface of antigen presenting cells, and can also specifically and rapidly respond to phosphoantigens, which is a set of nonpeptidic phosphorylated isoprenoid precursors.

In the Blood Atlas we have 16 gdTCR enriched genes and 2 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 169 genes are cell type group enriched and an additional 153 genes are enhanced in this cell type. Altogether, 338 genes are elevated and among these 88 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The gdTCR cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. Monocytes, and B-cells were eliminated by selecting CD14neg/CD19neg/CD3+ sub-population of lymphocytes (FSClow/SSClow). The gdTCR cells were sorted as gdTCR+/TCR Vα7.2neg cells, and 5,000 – 46,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing The transcriptome analysis shows that 53 % (n= 10383) of all human proteins (n=19,670) are expressed in the gdTCRs and 169 of these genes show an elevated expression in gdTCRs compared to the other 17 cell types (see figure below).

Figure 3. The distribution of all genes across the five specificity categories based on transcript abundance in gdTCR cells as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in gdTCR.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 13300 16
Group enriched 0341341 169
Cell type enhanced 3576411 153
Total 481131752 338

Table 6. The genes with the highest level of enriched expression in gdTCR. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of gdTCR expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
TMEM132C transmembrane protein 132C Detected in single 2.8 25
GALNT18 polypeptide N-acetylgalactosaminyltransferase 18 Detected in single 0.2 17
FBXO39 F-box protein 39 Detected in single 0.2 16
NFASC neurofascin Detected in single 0.1 14
HNF4G hepatocyte nuclear factor 4 gamma Detected in single 0.1 13
KRT84 keratin 84 Detected in single 0.1 12
CYP2C8 cytochrome P450 family 2 subfamily C member 8 Detected in single 0.3 9
LIM2 lens intrinsic membrane protein 2 Detected in some 16.2 8
GSC goosecoid homeobox Detected in single 4.8 7
TFCP2L1 transcription factor CP2 like 1 Detected in single 0.8 7
KLKB1 kallikrein B1 Detected in single 0.1 7
AC012531.3 Detected in single 0.6 7

MAIT T-cells

Mucosal associated invariant T-cells (MAIT T-cells) are involved in innate immunity and the defence against microbial activity and infection, but they also support the adaptive immune response and are thought to have a role in some autoimmune diseases.

In the Blood Atlas we have 44 MAIT T-cell enriched genes and 8 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 167 genes are cell type group enriched and an additional 147 genes are enhanced in this cell type. Altogether, 358 genes are elevated and among these 85 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The MAIT T-cells were isolated from PBMCs. Debris and cell aggregates were eliminated by gating based on scatter profiles. Monocytes, and B-cells were eliminated by selecting CD14neg/CD19neg/CD3+ sub-population of lymphocytes (FSClow/SSClow). MAIT T-cells were sorted as gdTCRneg/TCR Vα7.2+/CD161+ cells and 3,800 – 12,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 52 % (n= 10227) of all human proteins (n=19,670) are expressed in the MAIT T-cells and 167 of these genes show an elevated expression in MAIT T-cells compared to the other 17 cell types (see figure below).

Figure 4. The distribution of all genes across the five specificity categories based on transcript abundance in MAIT T-cells as well as in the other 17 cell types.

Table 7. Number of genes in the subdivided categories of elevated expression in MAIT T-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 241820 44
Group enriched 0371291 167
Cell type enhanced 4665360 147
Total 701201671 358

Table 8. The genes with the highest level of enriched expression in MAIT T-cells."pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of MAIT T-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
DAB2IP DAB2 interacting protein Detected in single 0.6 16
TUSC3 tumor suppressor candidate 3 Detected in single 0.2 15
TBL1Y transducin beta like 1 Y-linked Detected in single 0.1 14
FERMT2 fermitin family member 2 Detected in single 1.2 12
CFAP157 cilia and flagella associated protein 157 Detected in single 0.1 11
NTN4 netrin 4 Detected in single 2.0 11
DUOXA1 dual oxidase maturation factor 1 Detected in single 0.3 10
PRSS35 serine protease 35 Detected in some 25.1 9
TRPC3 transient receptor potential cation channel subfamily C member 3 Detected in single 0.2 9
ME1 malic enzyme 1 Detected in some 20.8 8
SLC4A10 solute carrier family 4 member 10 Detected in some 83.2 8
ITPKA inositol-trisphosphate 3-kinase A Detected in single 1.9 8

Naive CD4 T-cells

NaiveT-cells are located predominantly in lymphoid tissue and are mature T-cells that have not yet encountered its cognate antigen. Upon antigen activation they may further differentiate to memory T-cells.

In the Blood Atlas we have 20 naive CD4 T-cell enriched genes and 3 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 158 genes are cell type group enriched and an additional 173 genes are enhanced in this cell type. Altogether, 351 genes are elevated and among these 70 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The naive CD4 T-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. The naive CD4 T-cell population was sorted as CD3+/CD4+/CD8neg/CD45RA+ sub-population of lymphocytes (FSClow/SSClow). 10,000 – 77,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 52 % (n= 10218) of all human proteins (n=19,670) are expressed in the naive CD4 T-cells and 158 of these genes show an elevated expression in naive CD4 T-cells compared to the other 17 cell types (see figure below).

Figure 5. The distribution of all genes across the five specificity categories based on transcript abundance in naive CD4 T-cells as well as in the other 17 cell types.

Table 9. Number of genes in the subdivided categories of elevated expression in naive CD4 T-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 18110 20
Group enriched 0531041 158
Cell type enhanced 2590580 173
Total 431441631 351

Table 10. The genes with the highest level of enriched expression in naive CD4 T-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of naive CD4 T-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
CAPN9 calpain 9 Detected in single 0.2 17
OR2T34 olfactory receptor family 2 subfamily T member 34 Detected in single 0.1 15
PHKA1 phosphorylase kinase regulatory subunit alpha 1 Detected in single 0.1 14
ALB albumin Detected in single 0.1 13
KRT72 keratin 72 Detected in single 0.3 13
CAPSL calcyphosine like Detected in single 0.1 13
SORCS3 sortilin related VPS10 domain containing receptor 3 Detected in single 0.6 12
FAM78B family with sequence similarity 78 member B Detected in single 0.1 12
GRIA3 glutamate ionotropic receptor AMPA type subunit 3 Detected in single 0.0 9
WFDC10A WAP four-disulfide core domain 10A Detected in single 0.1 7
WFDC13 WAP four-disulfide core domain 13 Detected in single 0.7 7
GYS2 glycogen synthase 2 Detected in single 0.1 7

Memory CD4 T-cells

Memory T-cells provide the immune system with an effective defence against previously encountered pathogens, by having a long lifespan and the ability to quickly expand to large numbers upon re-exposure to their cognate antigen.

In the Blood Atlas we have 10 memory CD4 T-cell enriched genes and 0 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 176 genes are cell type group enriched and an additional 60 genes are enhanced in this cell type. Altogether, 246 genes are elevated and among these 60 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The memory CD4 T-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. The memory CD4 T-cell population was sorted as CD3+/CD4+/CD8neg/CD45RAneg sub-population of lymphocytes (FSClow/SSClow). 10,000 – 53,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 53 % (n= 10340) of all human proteins (n=19,670) are expressed in the memory CD4 T-cells and 176 of these genes show an elevated expression in memory CD4 T-cells compared to the other 17 cell types (see figure below).

Figure 6. The distribution of all genes across the five specificity categories based on transcript abundance in memory CD4 T-cells as well as in the other 17 cell types.

Table 11. Number of genes in the subdivided categories of elevated expression in memory CD4 T-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 9100 10
Group enriched 0491261 176
Cell type enhanced 134070 60
Total 22901331 246

Table 12. The genes with the highest level of enriched expression in memory CD4 T-cells."pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of memory CD4 T-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
IGFL2 IGF like family member 2 Detected in single 0.4 24
SPACA6 sperm acrosome associated 6 Detected in single 0.1 15
KRTAP4-3 keratin associated protein 4-3 Detected in single 0.1 15
NDP NDP, norrin cystine knot growth factor Detected in single 0.2 14
ADAM23 ADAM metallopeptidase domain 23 Detected in single 2.6 14
IL20RA interleukin 20 receptor subunit alpha Detected in single 0.1 13
ART5 ADP-ribosyltransferase 5 Detected in single 0.0 11
CYP4B1 cytochrome P450 family 4 subfamily B member 1 Detected in single 0.1 11
PRY PTPN13-like, Y-linked Detected in single 0.3 6
NEFL neurofilament light Detected in some 15.3 5

Naive CD8 T-cells

NaiveT-cells are located predominantly in lymphoid tissue and are mature T-cells that have not yet encountered its cognate antigen. Upon antigen activation they may further differentiate to memory T-cells.

In the Blood Atlas we have 19 naive CD8 T-cell enriched genes and 1 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 195 genes are cell type group enriched and an additional 97 genes are enhanced in this cell type. Altogether, 311 genes are elevated and among these 76 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The naive CD8 T-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. The naive CD8 T-cell population was sorted as CD3+/CD4neg/CD8+/CD45RA+ sub-population of lymphocytes (FSClow/SSClow). 10,000 – 77,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 53 % (n= 10398) of all human proteins (n=19,670) are expressed in the naive CD8 T-cells and 195 of these genes show an elevated expression in naive CD8 T-cells compared to the other 17 cell types (see figure below).

Figure 7. The distribution of all genes across the five specificity categories based on transcript abundance in naive CD8 T-cells as well as in the other 17 cell types.

Table 13. Number of genes in the subdivided categories of elevated expression in naive CD8 T-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 14500 19
Group enriched 0581361 195
Cell type enhanced 2858110 97
Total 421211471 311

Table 14. The genes with the highest level of enriched expression in naive CD8 T-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of naive CD8 T-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
PRM3 protamine 3 Detected in single 0.6 28
SLC7A3 solute carrier family 7 member 3 Detected in single 0.1 16
PCDHGB1 protocadherin gamma subfamily B, 1 Detected in single 0.1 14
CFAP97D2 CFAP97 domain containing 2 Detected in single 4.8 12
NDNF neuron derived neurotrophic factor Detected in single 0.0 11
GAP43 growth associated protein 43 Detected in single 0.2 10
MXRA8 matrix remodeling associated 8 Detected in some 7.8 7
ZCCHC12 zinc finger CCHC-type containing 12 Detected in single 1.4 6
CD248 CD248 molecule Detected in some 25.7 6
NRCAM neuronal cell adhesion molecule Detected in single 2.5 6
REG4 regenerating family member 4 Detected in some 26.9 6
MAOB monoamine oxidase B Detected in single 0.1 5

Memory CD8 T-cells

Memory T-cells provide the immune system with an effective defence against previously encountered pathogens, by having a long lifespan and the ability to quickly expand to large numbers upon re-exposure to their cognate antigen.

In the Blood Atlas we have 11 memory CD8 T-cell enriched genes and 2 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 176 genes are cell type group enriched and an additional 66 genes are enhanced in this cell type. Altogether, 253 genes are elevated and among these 82 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The memory CD8 T-cells were isolated from PBMCs. Debris and cell aggregates were eliminated based on scatter profiles. The memory CD8 T-cell population was sorted as CD3+/CD4neg/ CD8+/CD45RAneg sub-population of lymphocytes (FSClow/SSClow). 7,000 – 21,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 53 % (n= 10327) of all human proteins (n=19,670) are expressed in the memory CD8 T-cells and 176 of these genes show an elevated expression in memory CD8 T-cells compared to the other 17 cell types (see figure below).

Figure 8. The distribution of all genes across the five specificity categories based on transcript abundance in memory CD8 T-cells as well as in the other 17 cell types.

Table 15. Number of genes in the subdivided categories of elevated expression in memory CD8 T-cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 11000 11
Group enriched 0391361 176
Cell type enhanced 2135100 66
Total 32741461 253

Table 16. The genes with the highest level of enriched expression in memory CD8 T-cells. "pTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change ofmemory CD8 T-cell expression to the second highest cell type.

Gene Description Cell type distribution pTPM Specificity score
CH25H cholesterol 25-hydroxylase Detected in single 0.2 18
OR4A47 olfactory receptor family 4 subfamily A member 47 Detected in single 0.1 13
NKX2-3 NK2 homeobox 3 Detected in single 0.1 12
IRGC immunity related GTPase cinema Detected in single 0.1 12
IFNA21 interferon alpha 21 Detected in single 0.1 12
OVOL1 ovo like transcriptional repressor 1 Detected in single 0.1 12
OGDHL oxoglutarate dehydrogenase like Detected in single 0.1 11
NR2F2 nuclear receptor subfamily 2 group F member 2 Detected in single 0.1 11
PCDHB15 protocadherin beta 15 Detected in single 0.0 10
FAM180B family with sequence similarity 180 member B Detected in single 0.1 5
KRT74 keratin 74 Detected in single 0.0 4