Vol 54, No 2 (2023)
Original research article
Published online: 2023-03-24

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Long-term allogeneic hematopoietic cells transplantation survivors’ proinflammatory cytokine profiles compared to their respective donors and immunophenotype differences depending on GvHD history and infection status

Michał C. Czarnogórski1, Mateusz Maziewski2, Katarzyna Ruckemann-Dziurdzińska2, Justyna Sakowska3, Maciej Zieliński3, Jacek M. Witkowski2, Piotr Trzonkowski3, Magdalena Dutka1, Agnieszka Piekarska1, Igor Obuchowski4, Mikołaj Młyński1, Alicja Sadowska-Klasa1, Ewa Zarzycka1, Maria Bieniaszewska1, Andrzej Hellmann1, Jan Maciej Zaucha1
Acta Haematol Pol 2023;54(2):86-92.

Abstract

Introduction: In the course of allogeneic hematopoietic cell transplantation (allo-HCT) the donor’s hematopoietic progenitor cells are exposed to immense proliferative stress to reconstitute in the recipient the functional hematopoiesis. Moreover, recipients who develop infections or chronic graft-versus-host disease (GvHD) are subjected to further proliferative stress, especially in the lymphocyte subset. We hypothesized that allo-HCT may induce changes in proinflammatory cytokines profile and immunophenotype in the allo-HCT recipients, especially in patients with a chronic GvHD history. Material and methods: We compared the cytokine profile [interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α)] between long-term allo-HCT recipients and their respective donors and we analyzed cytokine profiles and the immunophenotype of lymphocytes in long-term recipients grouped according to their infection and GvHD history. Results: We found no differences in the proinflammatory cytokines between allo-HCT recipients and their respective donors, or between recipients grouped according to their infectious risk status. Immunophenotyping of recipients grouped according to their GvHD status revealed an increased percentage of B-cell presenting programmed death-1 in recipients without a history of GvHD. Conclusions: A lack of differences in proinflammatory cytokines concentrations between recipients and donors of allo-HCT would suggest that allo-HCT does not induce acceleration of the ‘inflammaging’-resembling phenomenon. No differences in the cytokine profile and immunophenotype between recipients grouped according to infectious risk status suggest that infectious risk is not reflected by the immunophenotype and cytokine profile. Furthermore, the lack of significant differences in immunophenotype of the recipients grouped according to a history of GvHD may suggest that in long-term survivors the immune system tends to stabilize with time.

ORIGINAL RESEARCH ARTICLE

Acta Haematologica Polonica 2023

Number 2, Volume 54, pages 88–92

DOI: 10.5603/AHP.a2023.0011

ISSN 0001–5814

e-ISSN 2300–7117

Long-term allogeneic hematopoietic cells transplantation survivors’ proinflammatory cytokine profiles compared to their respective donors and immunophenotype differences depending on GvHD history and infection status

Michał C. Czarnogórski1*Mateusz Maziewski2Katarzyna Ruckemann-Dziurdzińska2Justyna Sakowska3Maciej Zieliński3Jacek M. Witkowski2Piotr Trzonkowski3Magdalena Dutka1Agnieszka Piekarska1Igor Obuchowski4Mikołaj Młyński1Alicja Sadowska-Klasa1Ewa Zarzycka1Maria Bieniaszewska1Andrzej Hellmann1Jan Maciej Zaucha1
1Department of Hematology and Transplantology, Medical University of Gdańsk, Gdańsk, Poland
2Department of Physiopathology, Medical University of Gdańsk, Gdańsk, Poland
3Department of Medical Immunology, Medical University of Gdańsk, Gdańsk, Poland
4Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk and University of Gdańsk, Poland

*Address for correspondence: Michał C. Czarnogórski, Department of Hematology and Transplantology, Medical University of Gdańsk, Skłodowskiej-Curie 3a, 80–210 Gdańsk, Poland, e-mail: mcczarnogorski@gmail.com

Received: 09.11.2022 Accepted: 09.01.2023 Early publication date: 24.03.2023

Abstract
Introduction: In the course of allogeneic hematopoietic cell transplantation (allo-HCT) the donor’s hematopoietic progenitor cells are exposed to immense proliferative stress to reconstitute in the recipient the functional hematopoiesis. Moreover, recipients who develop infections or chronic graft-versus-host disease (GvHD) are subjected to further proliferative stress, especially in the lymphocyte subset. We hypothesized that allo-HCT may induce changes in proinflammatory cytokines profile and immunophenotype in the allo-HCT recipients, especially in patients with a chronic GvHD history.
Material and methods: We compared the cytokine profile [interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α)] between long-term allo-HCT recipients and their respective donors and we analyzed cytokine profiles and the immunophenotype of lymphocytes in long-term recipients grouped according to their infection and GvHD history.
Results: We found no differences in the proinflammatory cytokines between allo-HCT recipients and their respective donors, or between recipients grouped according to their infectious risk status. Immunophenotyping of recipients grouped according to their GvHD status revealed an increased percentage of B-cell presenting programmed death-1 in recipients without a history of GvHD.
Conclusions: A lack of differences in proinflammatory cytokines concentrations between recipients and donors of allo-HCT would suggest that allo-HCT does not induce acceleration of the ‘inflammaging’-resembling phenomenon. No differences in the cytokine profile and immunophenotype between recipients grouped according to infectious risk status suggest that infectious risk is not reflected by the immunophenotype and cytokine profile. Furthermore, the lack of significant differences in immunophenotype of the recipients grouped according to a history of GvHD may suggest that in long-term survivors the immune system tends to stabilize with time.
Key words: GvHD, cytokines, allo-HCT, immunophenotype
Acta Haematologica Polonica 2023; 54, 2: 86–92

Introduction

The introduction of allogeneic hematopoietic cell transplantation (allo-HCT) as a standard method of treatment for several malignant and non-malignant hematological diseases has created an excellent platform upon which to study human immunology and cell senescence. Since only a small percentage of the donor stem cells pool is collected and infused into the donor to engraft and reconstitute hematopoiesis, the cells are exposed to immense proliferative stress.

However, successful allo-HCT requires also that two important immunological barriers be overcome: host versus graft and graft versus host. Graft-versus-host reaction results from the exposure of lymphoid donor cells to the recipient antigens which induce donor lymphocyte activation and proliferation. Partially in patients with malignant diseases, this reaction is responsible for HCT’s success in eradicating the residual malignant cells (graft-versus-leukemia reaction). However, it may also lead to undesirable complications such as graft-versus-host disease (GvHD) resembling autoimmune diseases affecting several host organs. To prevent and control symptoms of graft versus host reaction, immunosuppressive agents disrupting lymphocyte proliferation (such as methotrexate and calcineurin inhibitors) are routinely administered after transplantation. A key role in GvHD is played by donor T cell lymphocytes but also B-lymphocytes [1, 2]. Involved donor lymphocytes undergo an additional intensive proliferation which may contribute to the accelerated telomere shortening in donor lymphocytes.

All of the above lead to the immense proliferative activity of the cells, including lymphocytes in allo-HCT recipients. We hypothesized that this could lead not only to accelerated telomeric shortening but also to immunophenotypic changes characteristic of natural aging. Healthy human ageing process includes in its characteristics the phenomenon of ‘inflammaging’. It may be defined as chronic, low-grade inflammation, without the presence of infection. In biochemical evaluation it presents with increased concentrations of proinflammatory cytokines due to antigenic stimulation over a lifespan of an individual [2].

It is also well known that the concentration of some proinflammatory cytokines [such as tumor necrosis fac­tor α (TNF-α), interleukin (IL)-6] increases, whereas others decrease (such as IL-10) during the course of chronic GvHD [3–5].

We reported recently our observations regarding the changes in immunophenotype and shortened telomeres in CD8+ lymphocyte subpopulation in long-term allo-HCT recipients compared to their respective donors [6]. Here, we present data on the proinflammatory cytokine profile of the same population of patients, i.e. long-term recipients of allo-HCT and their respective donors, to determine whether allo-HCT led to the changes in the proinflammatory cytokines. Moreover, we compared the immunophenotype of the recipients grouped according to their infection and cGvHD status.

Material and methods

The content of the materials and methods section were adapted from Czarnogórski et al. 2022 [6].

Patients

The study consist of 20 allo-HCT recipient-donor pairs. The span from the transplantation was more than 12 years ago. The study was conducted at University Clinical Center, Medical University of Gdansk. From all participants full venous blood sample was collected (50 mL).

GvHD and infectious status assessment

Patients were stratified according to their history of chronic GvHD status (yes vs. no) and infectious complications according to an infection risk status score developed for the purpose of this study [6].

Peripheral blood mononuclear cells and lymphocyte isolation

Perpheral blood mononuclear cells collection was performed from full venous blood with Ficoll-Hypaque centrifugation technique. Following lymphocyte isolation was performed by immunomagnetic separation. The lymphocyte subpopulations were TCD4+, TCD8+, B-lymphocytes and natural killers (NK) cells. The quality of collected material was assessed according to validated protocols [7, 8].

Proinflammatory cytokine concentrations

Proinflammatory cytokines concentrations (IL-1B, IL-2, IL-4, IL-6, IL-10, TNF-α and IL-17F) were assessed with flow cytometry. The results which did not reach the reference were excluded from the study.

Immunophenotyping

Immunophenotyping was performed according to protocol used by Czarnogórski et al. [6].

Statistical analysis

The statistical analysis was performed by STATISTICA 12.0 and with Microsoft Exel, detailed analysis was described according to Czarnogórski et al. [6]. The W Shapiro-Wilk test, and the Leven’s (Brown-Forsythe) test were used. The significance of differences between the two groups (independent samples model) was tested by Student’s t-test or by U Mann-Whitney. The significance of differences between more than two groups was verified using the Kruskal-Wallis test. In the case of receiving statistically significant differences between groups, the Dunn test was performed. A p value <0.05 was considered significant.

Results

Patient characteristics

The time from Tx to full venous blood cytometric analysis was at least 12 years with range 12–25 years (median 17.4 years). The population studied consisted of 12 males and 8 females. The prevalence of chronic graft versus host disease among recipients was 40%. Infection risk status was assessed according to Czarnogórski et al. [6]: 12 low risk recipients and 8 high risk recipients.

Proinflammatory cytokine concentrations

Surprisingly, we have found no statistically significant differences in the concentrations of the cytokines: TNF-α, IL-6, IL-10 (Table I). The results of assessment of IL-17F, IL-1β, IL-4, IL-2 concentrations were out of range, therefore they could not be included into analysis.

Table I. Recipients and donors of hematopoietic cell transplantation — cytokines concentrations

Parameter

R

D

p value

IL-6 [ng/L]:

N = 20

N = 20

0.5792*

  • avr (standard deviation)

0.99 (1.17)

1.61 (2.37)

  • range

0.38–5.42

0.07–9.53

  • median

0.58

0.72

  • 95% CI

0.44–1.54

0.50–2.72

IL-10 [ng/L]:

N = 19

N = 18

0.5333*

  • avr (standard deviation)

0.58 (0.69)

0.72 (0.71)

  • range

0.01–3.20

0.15–3.04

  • median

0.42

0.52

  • 95% CI

0.25–0.91

0.36–1.07

TNF-α [ng/L]:

N = 18

N = 19

0.3234*

  • avr (standard deviation)

0.77 (1.53)

0.83 (1.91)

  • range

0.01–6.78

0.02–8.51

  • median

0.33

0.22

  • 95% CI

0.01–1.54

–0.09–1.75

Neither we have found any differences between recipients when grouped according to infection risk status (Table II).

Table II. Recipients grouped according to infection risk status — cytokines concentrations

Parameter

Low risk

Intermediate/
/high risk

p value

IL-6 [ng/L]:

N = 12

N = 8

0.3159*

  • avr (standard deviation)

1.19 (1.49)

0.69 (0.20)

  • range

0.38–5.42

0.48–1.10

  • median

0.52

0.61

  • 95% CI

0.24–2.14

0.52–0.86

IL-10 [ng/L]:

N = 11

N = 8

0.9671*

  • avr (standard deviation)

0.68 (0.88)

0.45 (0.27)

  • range

0.01–3.20

0.11–0.87

  • median

0.48

0.39

  • 95% CI

0.09–1.27

0.23–0.67

TNF-α [ng/L]:

N = 12

N = 6

0.1898*

  • avr (standard deviation)

1.02 (1.85)

0.28 (0.20)

  • range

0.09–6.78

0.01–0.62

  • median

0.37

0.28

  • 95% CI

–0.15–2.19

0.07–0.49

Immunophenotype of allo-HCT recpients grouped according to chronic GvHD history

The analysis of immunophenotype of the allo-HCT recipients grouped according to cGvHD history showed no significant differences (see Supplementary Table 1), with the exception of a few parameters such as Treg Helios-Eomes+, B1 PD1+, B2 PD1+ and C19 PD1+. Lymphocytes B in recipients of allo-HCT who did not develop cGvHD had greater expression of PD-1 (Table III).

Table III. Recipients grouped according to chronic graft-versus-host disease (cGvHD) status — immunophenotype

Parameter

cGvHD

Without cGvHD

p value

Treg Helios–Eomes:

0.0227

  • avr (standard deviation)

4.1 (1.3)

8.7 (4.8)

  • range

2.4–5.4

4.2–19.1

  • median

4.6

7.2

  • 95% CI

2.7–5.5

5.2–12.1

B1 PD1:

0.0147

  • avr (standard deviation)

4.0 (2.7)

10.4 (5.5)

  • range

0.2–8.7

3.6–18.7

  • median

3.7

9.7

  • 95% CI

1.2–6.9

6.4–14.3

B2 PD1:

0.0448

  • avr (standard deviation)

0.7 (0.7)

1.8 (1.8)

  • range

0.1–2.1

0.6–6.2

  • median

0.5

1.1

CD19 PD1:

0.0147

  • avr (standard deviation)

1.2 (0.9)

3.3 (2.3)

  • range

0.2–2.9

1.2–8.9

  • median

0.9

3.0

  • 95% CI

0.2–2.2

1.6–4.9

Discussion

In this study, we tried to answer the question of whether allo-HCT accelerates the aging of the hematopoietic system by determining the differences in cytokine profile between long-term allo-HCT survivors and their respective donors of allo-HCT.

Studying donor-recipient pairs creates a unique model in which donor cells remaining in the donor could be compared to the donor cells infused into respective recipients. We were particularly interested in the features of postulated ‘inflammaging’. We also compared the same cytokine profile of the recipients when grouped according to infectious status (low vs intermediate/high) (see Czarnogórski et al. [6]). We hypothesized that allo-HCT recipients should have higher concentrations of proinflammatory cytokines as a robust indicator of aging. We also hypothesized that low-risk recipients according to their infection status would have increased concentrations of the same cytokines as an adaptation for fighting the infections.

Physiologically, the proinflammatory cytokine profile of older people is characterized by increased concentrations of the aforementioned cytokines (IL-1B, IL-2, IL-4, TNF-α, IL-6, IL-10, IL-15, IL-17, IL-18). These concentrations however do not exceed the upper reference range. Hence, inflammaging is defined as the process of chronic, sterile, low-grade inflammation.

There is no data on inflammaging in a population of allo-HCT survivors compared to their respective recipients serving as controls. We did not find any statistically significant differences in IL-6, IL-10 and TNF-α concentrations, either between main groups (recipients vs. donors) nor between recipients grouped according to infection risk status. Our data did not confirm our initial hypothesis that allo-HCT accelerates the inflammaging-resembling process.

We also did not find any differences between low and intermediate/high risk recipients stratified by their infection status, which could imply that infectious risk is not directly connected to the efficacy of one’s innate immune response. It would imply that allogeneic hematopoietic cells transplantation by itself does not impact the inflammaging [9]. However, the issue remains controversial since chronic low-grade inflammation (inflammaging) is a well-established risk factor for developing neoplasia [10, 11] which could be debatable in the population of our allo-HCT survivors since they were diagnosed with hematological malignancies in their 20 s and 30 s. On the other hand, there is ample data on the reduction of relapse risk after allo-HCT in patients who developed chronic GvHD that is in fact a chronic inflammation [12]. Moreover, it is difficult to differentiate if heightened concentrations of proinflammatory cytokines after allo-HCT result from chronic GvHD [13] or possibly are an adaptation for fighting the infection. There is some data correlating the occurrence of inflammaging and immune exhaustion in some hematological malignancies, such as plasmocytic myeloma [14]. Thus, it is challenging to determine whether the inflammaging features are due to older age or to the neoplasia itself.

Surprisingly, the incidence of chronic GvHD also did not impact any studied parameters, especially immunophenotype with the exception of B-cells expressing PD-1 which serves as the programmed death ligand-1 (PD-L1) receptor and plays a role in modulating immune response [15]. We also found no differences in T-cells expressing PD-1. An increased percentage of B-cells presenting PD-1 in recipients without chronic GvHD in anamnesis is difficult to interpret. Those differences in receptor expression in antigen-presenting cells (APCs) such as B-cells seem to be insignificant or accidental. The lack of differences in long-term (12 years+ from Tx) recipients of allo-HCT when grouped according to cGvHD history may suggest that the immune system tends to stabilize in the years following Tx. Many factors might explain such notion, that is immune suppression used, history of chronic degenerative diseases, GvHD resolution and small number of participants. Our study has several limitations. Firstly, it was performed in long-term survivors who were able to fight infections successfully and whose cGvHD status became stable. Secondly, the results are affected by the small population (20 pairs) and unfortunately the results of some cytokines assays were out of range, which might be related to laboratory errors. Unfortunately, we were unable to repeat tests with out-of-range results due to sample destruction during an electricity outage. Nevertheless, our results may suggest that allo-HCT does not accelerate the aging of the hematopoietic system despite a clear reduction of telomere shortening in specific cell populations and some immunophenotypic differences reported by us [6].

Authors’ contributions

All authors revised manuscript and read and approved final manuscript. MCC and JMZ wrote manuscript. MCC, PT, JMW, MD, JMZ were responsible for study design. MCC, AP, AS, JMZ, EZ, MB, MD, AH took part in patient recruitment and clinical data acquisition. MCC, IO, JMW, JMZ, MM and KRD performed laboratory and clinical data analysis. MC, JS, MM, MZ, JMW and PT performed laboratory work.

Conflict of interest

The authors declare no conflict of interest.

Financial support

Grants from the National Science Centre, Poland (No. 2018/31/N/NZ3/01035 awarded to MCC and 2019/03/X/NZ3/01848 awarded to MD).

Ethics

This study was approved by the Ethics Committee at the Medical University of Gdańsk — NKBBN/394-594/2019 and NKBBN/394-45/2020. Each participant signed an informed consent form.

Supplementary Table 1. Comparative characteristics of allogeneic hematopoietic cell transplantation recipients immunophenotype when grouped according to graft-versus-host disease status

Parameter

p value

Parameter

p value

Parameter

p value

B1

0.1193

NK CD39

0.5508

B1 PD1

0.0147

B2

0.0973

NK CD56 dim

0.2548

B2

0.2123

CD19

0.6511

NK CD56 high

0.2548

B2 Fas

0.9567

CD3

0.9599

NK Eomes

0.9567

B2 PD1

0.0448

DNT

0.4808

NK Perforin

0.7042

CD19

0.9567

NK

0.7595

NKT like

1.00

CD19 Fas

0.9567

NK CD56 dim

0.9512

Q1

0.5508

CD19 PD1

0.0147

NK CD56 high

0.4624

Q1 CD39

0.8708

CD4 CD27+CD28–

0.3290

NKT like

0.0662

Q1 Eomes

0.3566

CD4 CD27+CD28+

0.2123

T CD4

0.7250

Q1 IL10

0.5508

CD4 CD27–CD28–

0.4808

T CD8

0.9567

Q1 Perforin

0.0827

CD4 CD27–CD28+

0.7042

B1

0.0927

Q2

0.9567

CD4 CD28

0.3566

B1 CD39

0.4159

Q2 CD39

0.3028

CD4 CD57

0.3028

B1 Eomes

0.3566

Q2 Eomes

0.7863

CD4 FasL

0.8283

B1 IL10

0.1752

Q2 IL10

0.1585

CD4 PD-1

0.6255

B2

0.0927

Q2 Perforin

0.1752

CD8 CD27+CD28–

0.7683

B2 CD39

0.7449

Q3

0.3290

CD8 CD27+CD28+

0.1949

B2 Eomes

0.0577

Q3 CD39

0.7042

CD8 CD27–CD28–

0.6800

B2 IL10

0.6255

Q3 Eomes

0.2123

CD8 CD27–CD28+

0.5959

CD19

0.4808

Q3 IL10

0.1931

CD8 CD28

0.7683

CD19 CD39

0.4159

Q3 Perforin

0.8708

CD8 CD57

0.6800

CD19 Eomes

0.0448

RTE

0.1158

CD8 PD-1

0.3165

CD19 IL10

0.4477

T CD4

0.7863

DNT

0.3566

CD3

0.6255

T CD8

0.7863

Memory B

0.0735

CD4 CD39

0.4808

Treg FoxP3

0.9567

NK

0.2123

CD4 CM

0.3028

Treg FoxP3 CD39

0.6255

NK CD27

0.7449

CD4 EM

0.7042

Treg FoxP3 Eomes

0.9136

NK CD28

0.8708

CD4 Eomes

1.00

Treg FoxP3 IL10

0.0735

NK CD56 dim

0.2123

CD4 IL10

0.5508

Treg FoxP3 Perforin

0.2548

NK CD56 high

0.5508

CD4 Naive

0.9567

Treg Helios–

0.6255

NK CD57

0.3566

CD4 Perforin

0.0577

Treg Helios– CD39

0.3566

NK PD-1

0.6255

CD4 Temra

0.7863

Treg Helios– Eomes

0.0227

NKT like

0.9567

CD8 CD39

0.8137

Treg Helios– IL10

0.1752

Q1

0.8708

CD8 CM

0.3768

Treg Helios– Perforin

0.2548

Q1 CD27

0.9567

CD8 EM

0.0875

Treg Helios+

0.7042

Q1 CD28

0.1431

CD8 Eomes

0.2159

Treg Helios+ CD39

0.7042

Q1 CD57

0.2123

CD8 Naive

0.2629

Treg Helios+ Eomes

0.0577

Q1 FasL

0.7863

CD8 Perforin

0.3768

Treg Helios+ IL10

0.0927

Q1 PD-1

0.3566

CD8 Temra

0.953

Treg Helios+ Perforin

0.6255

Q2

0.9567

DNT

0.4159

B1

0.2123

Q2 CD27

0.7449

NK

0.2123

B1 Fas

0.8708

Q2 CD28

0.5508

Q2 CD57

0.0735

CD3

0.9567

Treg FoxP3 CXCR5

0.1431

Q2 FasL

0.4159

CD4 CD152

0.6255

Treg FoxP3 TIGIT

0.7863

Q2 PD-1

0.9567

CD4 CXCR4

0.7042

Treg Helios–

0.4808

Q3

0.1158

CD4 CXCR5

0.1431

Treg Helios– CCR5

0.5508

Q3 CD27

0.3566

CD4 TIGIT

0.4477

Treg Helios– CD152

0.7042

Q3 CD28

0.7449

CD8 CXCR4

0.7683

Treg Helios– CXCR4

0.4159

Q3 CD57

0.0057

CD8 CXCR5

0.1116

Treg Helios– CXCR5

0.6255

Q3 FasL

0.1431

CD8 TIGIT

0.5169

Treg Helios– TIGIT

0.7042

Q3 PD-1

0.0577

DNT

0.4159

Treg Helios+

0.5508

T CD4

0.7042

NK

0.2123

Treg Helios+ CCR5

0.8708

T CD8

0.6255

NK CCR5

0.4477

Treg Helios+ CD152

0.7042

Treg FoxP3

0.9567

NK CD56 dim

0.2123

Treg Helios+ CXCR4

0.6255

Treg FoxP3 CD27

0.1037

NK CD56 high

0.4159

Treg Helios+ CXCR5

0.4808

Treg FoxP3 CD28

0.7042

NK CXCR4

0.2548

Treg Helios+ TIGIT

0.8708

Treg FoxP3 CD57

0.0735

NK CXCR5

0.3566

Treg FoxP3 FasL

0.1931

NK TIGIT

0.4808

Treg FoxP3 PD-1

0.4808

NKT like

0.9567

Treg Helios–

0.0735

Q1

0.5508

Treg Helios– CD27

0.9567

Q1 CCR5

0.4159

Treg Helios– CD28

0.3028

Q1 CD152

0.5876

Treg Helios– CD57

0.0577

Q1 CXCR4

0.8708

Treg Helios– FasL

0.2781

Q1 CXCR5

0.1431

Treg Helios– PD-1

0.4808

Q1 TIGIT

0.3028

Treg Helios+

0.7863

Q2

0.8708

Treg Helios+ CD27

0.1585

Q2 CCR5

0.9567

Treg Helios+ CD28

0.8708

Q2 CD152

0.3028

Treg Helios+ CD57

0.0079

Q2 CXCR4

0.4477

Treg Helios+ FasL

0.3028

Q2 CXCR5

0.9567

Treg Helios+ PD-1

0.7863

Q2 TIGIT

0.2548

B1

0.0927

Q3

0.4159

B1 CCR5

0.3566

Q3 CCR5

0.7863

B1 CD152

0.0735

Q3 CD152

0.6255

B1 CXCR5

0.2548

Q3 CXCR4

0.7042

B2

0.0577

Q3 CXCR5

0.4808

B2 CCR5

0.7449

Q3 TIGIT

0.6644

B2 CD152

0.3028

T CD4

0.8708

B2 CXCR5

0.4477

T CD8

0.8708

CD19

0.4159

Treg FoxP3

0.9567

CD19 CCR5

0.4159

Treg FoxP3 CCR5

0.7042

CD19 CD152

0.1752

Treg FoxP3 CD152

0.7042

CD19 CXCR5

0.7042

Treg FoxP3 CXCR4

1.00

References

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