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 Immune cell section we have 461 cell lineage enriched genes and 165 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 445 genes are cell lineage group enriched and an additional 16 genes are enhanced in this cell lineage. Altogether, 922 genes are elevated and among these 275 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Lineage enriched	184	0	82	26	292
	Group enriched	0	0	341	91	432
	Lineage enhanced	16	0	0	0	16
	Total	200	0	423	117	740

Table 2. The genes with the highest level of enriched expression in T-cell lineage. "nTPM" 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	nTPM	Specificity score
FANK1	fibronectin type III and ankyrin repeat domains 1	Detected in single	61.2	612
CTLA4	cytotoxic T-lymphocyte associated protein 4	Detected in single	44.5	445
FOXP3	forkhead box P3	Detected in single	53.3	394
ELOVL4	ELOVL fatty acid elongase 4	Detected in single	23.7	238
PRSS35	serine protease 35	Detected in single	19.5	195
CD248	CD248 molecule	Detected in single	21.8	144
NEFL	neurofilament light	Detected in single	11.2	113
CPA5	carboxypeptidase A5	Detected in single	56.4	102
REG4	regenerating family member 4	Detected in single	24.6	101
TMEM171	transmembrane protein 171	Detected in single	24.1	89
THEMIS	thymocyte selection associated	Detected in single	58.3	88
PMCH	pro-melanin concentrating hormone	Detected in single	9.5	85

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 Immune cell section we have 35 T-reg 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, 222 genes are cell type group enriched and an additional 168 genes are enhanced in this cell type. Altogether, 425 genes are elevated and among these 182 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 45 % (n= 9042) of all human proteins (n=20090) are expressed in the T-regs and 222 of these genes show an elevated expression in T-regs 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 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	15	14	6	0	35
	Group enriched	0	34	169	19	222
	Immune cell enhanced	28	39	93	8	168
	Total	43	87	268	27	425

Table 4. The genes with the highest level of enriched expression in T-reg cells. "nTPM" 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	nTPM	Specificity score
FANK1	fibronectin type III and ankyrin repeat domains 1	Detected in some	61.2	16
SEMA3G	semaphorin 3G	Detected in single	1.4	15
FOXP3	forkhead box P3	Detected in some	53.3	11
HACD1	3-hydroxyacyl-CoA dehydratase 1	Detected in many	55.7	11
ACTG2	actin gamma 2, smooth muscle	Detected in single	8.6	11
PMCH	pro-melanin concentrating hormone	Detected in some	9.5	10
DUSP4	dual specificity phosphatase 4	Detected in single	6.7	9
OGN	osteoglycin	Detected in single	1.7	9
TRIM16	tripartite motif containing 16	Detected in many	45.1	9
BOLL	boule homolog, RNA binding protein	Detected in single	1.5	9
RTKN2	rhotekin 2	Detected in some	16.7	8
CEP55	centrosomal protein 55	Detected in single	1.3	8

gdT-cells

Gamma delta T cells (gdT-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. gdT-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 Immune cell section we have 13 gdT-cell enriched genes and 5 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 140 genes are cell type group enriched and an additional 74 genes are enhanced in this cell type. Altogether, 227 genes are elevated and among these 74 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The gdT-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 45 % (n= 9081) of all human proteins (n=20090) are expressed in the gdTCRs and 140 of these genes show an elevated expression in gdT-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 gdT-cell cells as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in gdT-cell.

		Distribution in the 18 cell types
		Detected in single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	5	2	6	0	13
	Group enriched	0	15	105	20	140
	Immune cell enhanced	16	22	29	7	74
	Total	21	39	140	27	227

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

Gene	Description	Cell type distribution	nTPM	Specificity score
TMEM132C	transmembrane protein 132C	Detected in single	1.9	19
GSC	goosecoid homeobox	Detected in single	3.6	8
LIM2	lens intrinsic membrane protein 2	Detected in some	11.3	7
BNC2	basonuclin 2	Detected in single	2.5	5
KIR3DL1	killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1	Detected in single	1.8	4

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 Immune cell section we have 27 MAIT 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, 149 genes are cell type group enriched and an additional 64 genes are enhanced in this cell type. Altogether, 240 genes are elevated and among these 84 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 45 % (n= 9066) of all human proteins (n=20090) are expressed in the MAIT T-cells and 149 of these genes show an elevated expression in MAIT 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 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	13	9	5	0	27
	Group enriched	0	11	118	20	149
	Immune cell enhanced	8	27	26	3	64
	Total	21	47	149	23	240

Table 8. The genes with the highest level of enriched expression in MAIT T-cells."nTPM" 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	nTPM	Specificity score
NTN4	netrin 4	Detected in single	1.6	12
PRSS35	serine protease 35	Detected in some	19.5	9
TPBG	trophoblast glycoprotein	Detected in single	1.4	8
SLC4A10	solute carrier family 4 member 10	Detected in some	63.3	8
ITPKA	inositol-trisphosphate 3-kinase A	Detected in single	1.4	8
IL23R	interleukin 23 receptor	Detected in some	21.7	8
ME1	malic enzyme 1	Detected in some	16.0	7
TSPAN15	tetraspanin 15	Detected in many	19.5	6
ELOVL4	ELOVL fatty acid elongase 4	Detected in some	23.7	6
CYP27B1	cytochrome P450 family 27 subfamily B member 1	Detected in single	1.2	6
ROR2	receptor tyrosine kinase like orphan receptor 2	Detected in single	1.0	6
RORC	RAR related orphan receptor C	Detected in many	50.3	6

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 Immune cell section we have 1 naive 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, 203 genes are cell type group enriched and an additional 82 genes are enhanced in this cell type. Altogether, 286 genes are elevated and among these 124 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 45 % (n= 9000) of all human proteins (n=20090) are expressed in the naive CD4 T-cells and 203 of these genes show an elevated expression in naive 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 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	0	0	1	0	1
	Group enriched	0	28	159	16	203
	Immune cell enhanced	14	29	36	3	82
	Total	14	57	196	19	286

Table 10. The genes with the highest level of enriched expression in naive CD4 T-cells. "nTPM" 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	nTPM	Specificity score
FHIT	fragile histidine triad diadenosine triphosphatase	Detected in many	87.6	4

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 Immune cell section we have 2 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, 219 genes are cell type group enriched and an additional 23 genes are enhanced in this cell type. Altogether, 244 genes are elevated and among these 119 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 45 % (n= 9116) of all human proteins (n=20090) are expressed in the memory CD4 T-cells and 219 of these genes show an elevated expression in memory CD4 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 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	1	1	0	0	2
	Group enriched	0	25	176	18	219
	Immune cell enhanced	4	9	10	0	23
	Total	5	35	186	18	244

Table 12. The genes with the highest level of enriched expression in memory CD4 T-cells."nTPM" 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	nTPM	Specificity score
ADAM23	ADAM metallopeptidase domain 23	Detected in single	2.1	16
NEFL	neurofilament light	Detected in some	11.2	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 Immune cell section we have 8 naive CD8 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, 238 genes are cell type group enriched and an additional 29 genes are enhanced in this cell type. Altogether, 275 genes are elevated and among these 121 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 46 % (n= 9142) of all human proteins (n=20090) are expressed in the naive CD8 T-cells and 238 of these genes show an elevated expression in naive 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 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	5	3	0	0	8
	Group enriched	0	35	183	20	238
	Immune cell enhanced	8	15	6	0	29
	Total	13	53	189	20	275

Table 14. The genes with the highest level of enriched expression in naive CD8 T-cells. "nTPM" 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	nTPM	Specificity score
CFAP97D2	CFAP97 domain containing 2	Detected in single	4.0	12
CD248	CD248 molecule	Detected in some	21.8	7
MXRA8	matrix remodeling associated 8	Detected in single	6.4	7
ZCCHC12	zinc finger CCHC-type containing 12	Detected in single	1.2	6
NRCAM	neuronal cell adhesion molecule	Detected in single	2.0	6
REG4	regenerating family member 4	Detected in some	24.6	6
SFRP5	secreted frizzled related protein 5	Detected in single	3.6	4
MT3	metallothionein 3	Detected in some	5.0	4

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 Immune cell section we have 0 memory CD8 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, 227 genes are cell type group enriched and an additional 18 genes are enhanced in this cell type. Altogether, 245 genes are elevated and among these 126 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 46 % (n= 9155) of all human proteins (n=20090) are expressed in the memory CD8 T-cells and 227 of these genes show an elevated expression in memory CD8 T-cells compared to the other 17 cell types (see figure below).

Figure . 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 single	Detected in some	Detected in many	Detected in all	Total
Specificity	Immune cell enriched	0	0	0	0	0
	Group enriched	0	21	186	20	227
	Immune cell enhanced	1	8	8	1	18
	Total	1	29	194	21	245

Table 16. The genes with the highest level of enriched expression in memory CD8 T-cells. "nTPM" 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	nTPM	Specificity score