Characterization of CD8<sup>+</sup> T cell subsets in male and female non-obese diabetic mice

Shushu YANG; Dong LIU; Jie LI; Mengjun ZHANG; Li WANG

doi:10.16016/j.2097-0927.202312058

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Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice

Basic Medicine | 更新时间：2026-01-09

- Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice
- Journal of Army Medical University Vol. 46, Issue 8, Pages: 837-848(2024)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)：基础医学院免疫学教研室
  2.400038 重庆，陆军军医大学(第三军医大学)：药学与检验医学系药物分析学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Science Foundation of China(82071825);the General Program of National Natural Science Foundation of China(81871301)
- DOI：10.16016/j.2097-0927.202312058
  CLC： R339.2;R392.12;R587.1
- Received：11 December 2023，
  
  Revised：2024-01-10，
  
  Published：30 April 2024
- 稿件说明：
移动端阅览
Shushu YANG, Dong LIU, Jie LI, et al. Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice[J]. Journal of Army Medical University, 2024, 46(8): 837-848.
DOI：

Shushu YANG, Dong LIU, Jie LI, et al. Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice[J]. Journal of Army Medical University, 2024, 46(8): 837-848. DOI： 10.16016/j.2097-0927.202312058.

摘要

目的

以雌性和雄性非肥胖糖尿病(nonobese diabetic

NOD)小鼠以及健康对照癌症研究所(institute for cancer research

ICR)小鼠为研究对象，比较分析初始、效应、记忆、耗竭以及调节性CD8

T细胞分化亚群差异，探讨1型糖尿病(type 1 diabetes

T1D)背景下的性别因素对CD8

T细胞分化命运的影响。

方法

采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes

pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes

PIL)、初始T细胞(na?ve T cells

)、中枢记忆T细胞(central memory T cells

)、效应T细胞(effector T cells

EFF

)、效应前体样T细胞(effector precursor T cells

)、耗竭T细胞(exhausted T cells

)、耗竭前体T细胞(precursor exhausted T cells

PEX

)以及调节性T细胞(regulatory T cells

Tregs)等CD8

T细胞分化亚群的频率和表型差异。

结果

与雄性NOD小鼠比较，雌性NOD小鼠pLN及PIL中IFN-γ

、CD107a

和CCL5

CD8

EFF

频率显著升高(

0.01

0.05

0.05)，同时脾脏中CD8

、CD8

PEX

和CD122

CD8

Tregs亚群的频率均显著降低(

0.01

0.001)；而雌性和雄性ICR小鼠体内除CD122

CD8

Tregs差异变化与NOD小鼠一致(

0.05)，其余上述各CD8

T细胞分化亚群无显著差异。

结论

雄激素可能通过抑制记忆T细胞向效应T细胞分化，同时促进效应T细胞功能耗竭，导致雌雄发病率差异。

Abstract

Objective

To compare and analyze the differences in CD8

naive

effector

memory

exhausted and regulatory T cells in order to investigate the impact of gender on the differentiation fate of CD8

T cells in the context of type 1 diabetes (T1D) based on female and male non-obese diabetic (NOD) mice and healthy Institute for Cancer Research (ICR) mice.

Methods

The frequencies and phenotypes of CD8

T cell differentiation subsets including naive T cells (T

)

central memory T cells (T

)

effector T cells (T

EFF

)

effector precursor T cells (T

)

exhausted T cells (T

)

precursor exhausted T cells (T

PEX

) and regulatory T cells (Tregs) in the spleen

pancreatic draining lymph nodes (pLN) and pancreas infiltrating lymphocytes (PIL) of male and female NOD mice were detected by flow cytometry.

Results

The frequencies of IFN-γ

CD107a

and CCL5

CD8

EFF

in pLN and PIL of female NOD mice were significantly higher than those of

male NOD mice. However

the frequencies of CD8

CD8

PEX

and CD122

CD8

Tregs subsets in the spleen were significantly decreased. While there were no significant differences in the above CD8

T cell subsets except CD8

Tregs between female and male ICR mice.

Conclusion

Androgen may inhibit the differentiation of memory T cells into effector T cells and promote the exhaustion of effector T cells

leading to the difference in morbidity between the male and female mice.

关键词

Keywords

references

WENG J P, ZHOU Z G, GUO L X, et al . Incidence of type 1 diabetes in China, 2010-13: population based study[J ] . Br Med J, 2018, 360: j5295. DOI: 10.1136/bmj.j5295.

WENG J P, ZHOU Z G, GUO L X. Comment on Liu, et al. incidence of type 1 diabetes may be underestimated in the Chinese population: evidence from 21.7 million people between 2007 and 2017. diabetes care 2021;44: 2503-2509[J ] . Diabetes Care, 2022, 45(1): e12. DOI: 10.2337/dc21-1820 http://dx.doi.org/10.2337/dc21-1820 .

KLEIN S L, FLANAGAN K L. Sex differences in immune responses[J]. Nat Rev Immunol, 2016, 16(10): 626-638. DOI: 10.1038/nri.2016.90.

MOULTON V R. Sex hormones in acquired immunity and autoimmune disease[J]. Front Immunol, 2018, 9: 2279. DOI: 10.3389/fimmu.2018.02279.

VASANTHAKUMAR A, CHISANGA D, BLUME J, et al . Sex-specific adipose tissue imprinting of regulatory T cells[J ] . Nature, 2020, 579(7800): 581-585. DOI: 10.1038/s41586-020-2040-3.

SHEPHERD R, CHEUNG A S, PANG K, et al . Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics[J ] . Front Immunol, 2020, 11: 604000. DOI: 10.3389/fimmu.2020.604000.

YOUNG E F, HESS P R, ARNOLD L W, et al . Islet lymphocyte subsets in male and female NOD mice are qualitatively similar but quantitatively distinct[J ] . Autoimmunity, 2009, 42(8): 678-691. DOI: 10.3109/08916930903213993.

KIKUTANI H, MAKINO S. The murine autoimmune diabetes model: nod and related strains[J]. Adv Immunol, 1992, 51: 285-322. DOI: 10.1016/s0065-2776(08)60490-3.

YURKOVETSKIY L, BURROWS M, KHAN A A, et al . Gender bias in autoimmunity is influenced by microbiota[J ] . Immunity, 2013, 39(2): 400-412. DOI: 10.1016/j.immuni.2013.08.013.

GEARTY S V, DÜNDAR F, ZUMBO P, et al . An autoimmune stem-like CD8 T cell population drives type 1 diabetes[J ] . Nature, 2022, 602(7895): 156-161. DOI: 10.1038/s41586-021-04248-x.

AKTAS E, KUCUKSEZER U C, BILGIC S, et al . Relationship between CD107a expression and cytotoxicactivity[J ] . Cell Immunol, 2009, 254(2): 149-154. DOI: 10.1016/j.cellimm.2008.08.007.

COHNEN A, CHIANG S C, STOJANOVIC A, et al . Surface CD107a/LAMP-1 protects natural killer cells from degranu lation-associated damage[J ] . Blood, 2013, 122(8): 1411-1418. DOI: 10.1182/blood-2012-07-441832.

XIONG H, CUI M T, KONG N, et al . Cytotoxic CD161-CD8 + TEMRA cells contribute to the pathogenesis of systemic lupuserythematosus[J ] . EBioMedicine, 2023, 90: 104507. DOI: 10.1016/j.ebiom.2023.104507..

HINRICHS A C, BLOKLAND S L M, LOPES A P, et al . Transcriptome analysis of CCR9+ T helper cells from primary sjögren's syndrome patients identifies CCL5 asa novel effector molecule[J ] . Front Immunol, 2021, 12: 702733. DOI: 10.3389/fimmu.2021.702733.

LEQUEUX A, NOMAN M Z, XIAO M, et al . Targeting HIF-1 alpha transcriptional activity drives cytotoxic immune effector cells into melanoma and improves combination immunotherapy[J ] . Oncogene, 2021, 40(28): 4725-4735. DOI: 10.1038/s41388-021-01846-x.

SPRENT J, ZHANG X, SUN S, et al . T-cell proliferation in vivo and the role of cytokines[J ] . Philos Trans R Soc Lond B Biol Sci, 2000, 355(1395): 317-322. DOI: 10.1098/rstb.2000.0568.

GATTINONI L, ZHONG X S, PALMER D C, et al . Wnt signaling arrest s effector T cell differentiation and generates CD8 + memory stem cells[J ] . Nat Med, 2009, 15(7): 808-813. DOI: 10.1038/nm.1982..

NAKAJIMA Y, CHAMOTO K, OURA T, et al . Critical role of the CD44 low CD62L low CD8 + T cell subset in restoring antitumor immunity in aged mice[J ] . Proc Natl Acad Sci U S A, 2021, 118(23): e2103730118. DOI: 10.1073/pnas.2103730118..

HASHIMOTO M, KAMPHORST A O, IM S J, et al . CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions[J ] . Annu Rev Med, 2018, 69: 301-318. DOI: 10.1146/annurev-med-012017-043208.

WU T Q, JI Y, MOSEMAN E A, et al . The TCF1-Bcl6 axis counteracts type Ⅰ interferon to repress exhaustion and maintain T cell stemness[J ] . Sci Immunol, 2016, 1(6): eaai8593. DOI: 10.1126/sciimmunol.aai8593.

MCLANE L M, ABDEL-HAKEEM M S, WHERRY E J. CD8 T cell exhaustion during chronic viral infection and cancer[J]. Annu Rev Immunol, 2019, 37: 457-495. DOI: 10.1146/annurev-immunol-041015-055318.

WEISSHAAR N, WU J X, MING Y N, et al . Rgs16 promotes antitumor CD8 + T cell exhaustion[J ] . Sci Immunol, 2022, 7(71): eabh1873. DOI: 10.1126/sciimmunol.abh1873..

DAI Z, ZHANG S, XIE Q, et al . Natural CD8 + CD122 + T cells are more potent in suppression of allograft rejection than CD4 + CD25 + regulatory T cells[J ] . Am J Transplant, 2014, 14(1): 39-48. DOI: 10.1111/ajt.12515..

ARNDT B, WITKOWSKI L, ELLWART J, et al . CD8 + CD122 + PD-1-effector cells promote the development of diabetes in NOD mice[J ] . J Leukoc Biol, 2015, 97(1): 111-120. DOI: 10.1189/jlb.3A0613-344RR..

WANG F D, CHENG F J, ZHENG F. Stem cell like memory T cells: a new paradigm in cancer immunotherapy[J]. Clin Immunol, 2022, 241: 109078. DOI: 10.1016/j.clim.2022.109078.

GATTINONI L, LUGLI E, JI Y, et al . A human memory T cell subset with stem cell-like properties[J ] . Nat Med, 2011, 17(10): 1290-1297. DOI: 10.1038/nm.2446.

SMERDON R A, PEAKMAN M, HUSSAIN M J, et al . Increase in simultaneous coexpression of naive and memory lymphocyte markers at diagnosis of IDDM[J ] . Diabetes, 1993, 42( 1): 127-133. DOI: 10.2337/diab.42.1.127.

ZHANG Y, JOE G, HEXNER E, et al . Host-reactive CD8 + memory stem cells in graft-versus-host disease[J ] . Nat Med, 2005, 11(12): 1299-1305. DOI: 10.1038/nm1326..

KWON H, SCHAFER J M, SONG N J, et al . Androgen conspires with the CD8 + T cell exhaustion program and contributes to sex bias in cancer[J ] . Sci Immunol, 2022, 7(73): eabq2630. DOI: 10.1126/sciimmunol.abq2630..

GUAN X N, POLESSO F, WANG C J, et al . Androgen receptor activity in T cells limits checkpoint blockade efficacy[J ] . Nature, 2022, 606(7915): 791-796. DOI: 10.1038/s41586-022-04522-6

ANSARI M J, SALAMA A D, CHITNIS T, et al . The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice[J ] . J Exp Med, 2003, 198(1): 63-69. DOI: 10.1084/jem.20022125.

傅昭粤, 沈娱汀, 李娟, 等. +15Gz重复暴露对小鼠CD4 + T淋巴细胞的影响[J ] . 空军军医大学学报, 2023, 44(1): 42-47. DOI: 10.13276/j.issn.2097-1656.2023.01.008.

FU Z Y, SHEN Y T, LI J, et al . Effects o f repeated +15Gz exposure on mouse CD4 + T lymphocytes[J ] . J Air Force Med Univ, 2023, 44(1): 42-47. DOI: 10.13276/j.issn.2097-1656.2023.01.008..

STOCKSB T, WILSON C S, MARSHALL A F, et al . Regulation of diabetogenic immunity by IL-15-activated regulatory CD8 T cells in type 1 diabetes[J ] . J Immunol, 2019, 203(1): 158-166. DOI: 10.4049/jimmunol.1800976.

LIU H Z, WANG Y S, ZENG Q H, et al . Suppression of allograft rejection by CD8 + CD122 + PD-1+ Tregs is dictated by their Fas ligand-initiated killing of effector T cells versus Fas-mediated own apoptosis[J ] . Oncotarget, 2017, 8(15): 24187-24195. DOI: 10.18632/oncotarget.15551..

SHIMOKAWA C, KATO T, TAKEUCHI T, et al . CD8 + regulatory T cells are critical in prevention of autoimmune-mediated diabetes[J ] . Nat Commun, 2020, 11(1): 1922. DOI: 10.1038/s41467-020-15857-x..

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⁰

Characterization of CD8+ T cell subsets in male and female non-obese diabetic mice

DOI：10.16016/j.2097-0927.202312058

摘要

Abstract

关键词

Keywords

references

Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice