







































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: wwalana@uds.edu.gh; 
 
Cite as: Walana, Williams, George Billak, Jennifer Suurbaar, and Hawa Malechi. 2025. “T Cell Exhaustion and Immune 
Dysfunction in Spontaneous Abortion: A Targeted Review”. Asian Journal of Immunology 8 (1):179-89. 
https://doi.org/10.9734/aji/2025/v8i1170. 
 

 
 

Asian Journal of Immunology 
 
Volume 8, Issue 1, Page 179-189, 2025; Article no.AJI.139815 
 

 
 

 

 

T Cell Exhaustion and Immune 
Dysfunction in Spontaneous  
Abortion: A Targeted Review 

 
Williams Walana a*, George Billak b, Jennifer Suurbaar b  

and Hawa Malechi c,d 
 

a Department of Clinical Microbiology, School of Medicine, University for Development Studies, 
Tamale, Ghana. 

b Department of Biochemistry and Molecular Medicine, School of Medicine, University for 
Development Studies, Tamale, Ghana. 

c Department of Obstetrics and Gynaecology, School of Medicine, University for Development 
Studies, Tamale, Ghana. 

d Department of Obstetrics and Gynaecology, Tamale Teaching Hospital, Northern Region,  
Tamale, Ghana. 

 
Authors’ contributions  

 
This work was carried out in collaboration among all authors. Authors WW and GB conceived the 
idea. Authors WW, GB, JS and HM performed a literature search. All authors reviewed and made 

significant contributions to finalise the manuscript and agreed to the submission of this manuscript  
for consideration. All authors read and approved the final manuscript. 

 

Article Information 
 

DOI: https://doi.org/10.9734/aji/2025/v8i1170  
 

Open Peer Review History: 
This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers,  

peer review comments, different versions of the manuscript, comments of the editors, etc, are available here: 
https://pr.sdiarticle5.com/review-history/139815  

 
 

Received: 10/05/2025 
Published: 15/07/2025 

 
 

ABSTRACT 
 

Background: Immune tolerance is established between the foetus and the mother in normal 
pregnancies. However, this tolerance may be breached, resulting in undesired pregnancy 
outcomes such as spontaneous abortion, foetal anomalies, and maternal complications. Reported 

Review Article 

https://doi.org/10.9734/aji/2025/v8i1170
https://pr.sdiarticle5.com/review-history/139815


 
 
 
 

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studies suggest a potential link between immune response and unplanned pregnancy termination. 
A comprehensive understanding of immune responses in pregnancy loss harbours the potential to 
control the associated mechanisms.   
Objective: This review synthesised existing studies on T cell exhaustion (TCE) in spontaneous 
abortion and pregnancy complications. 
Methodology: A comprehensive database search from Scopus, Google Scholar, PubMed, and 
Web of Science identified 21 eligible studies that reported original data on spontaneous abortion 
and pregnancy complications and TCE.  
Results: The review has shown that TCE is common in spontaneous abortion, characterised by 
the upregulation of inhibitory receptors and a suboptimal or lack of T-cells to perform their normal 
functions, such as proliferation, cytokine production, and cytotoxicity. Decreased expression of PD-
1, LAG-3 and Tim-3 may contribute to an enhanced inflammatory response. Increased proportions 
of Th1 and Th17 cells are associated with pro-inflammatory responses and decreased immune 
regulatory function, resulting from altered PD-1/PD-L1 expression, which may contribute to 
pregnancy loss. Decreased anti-inflammatory cytokines (TGF-β1, IL-10, and IL-4) promote an 
imbalanced homeostasis, which can lead to pregnancy loss. These anomalies are partly anchored 
on chronic antigen exposure, oxidative stress, and hormonal changes, phenomena frequently 
associated with recurrent spontaneous abortion or poor pregnancy outcomes.   
Conclusion: Optimal modulation of immune response to control TCE may prevent or minimise the 
occurrence of spontaneous abortion and promote successful pregnancies. 
 

 

Keywords: T cell exhaustion; immune exhaustion; spontaneous abortion; pregnancy; immune 
regulation; reproductive immunology; systematic review. 

 

1. INTRODUCTION 
 
Pregnancy is a complex immune state where 
tolerance and immune activation coexist (Hu et 
al., 2016). Despite its prevalence, the 
mechanisms governing maternal-foetal immune 
tolerance remain unclear. Pregnancy failure 
affects approximately 15% of known 
pregnancies, with more than 50% attributed to 
immune tolerance defects (Kuon et al., 2015). 
Research has shown that natural killer cells 
expressing Tim-3 play a defensive role in the 
early stages of pregnancy, promoting 
immunosuppressive activities and the induction 
of regulatory T cells (Kuon et al., 2015). 

 
Spontaneous abortion, also known as 
miscarriage, is the unplanned termination of a 
pregnancy before the foetus can survive outside 
the womb, typically before the 20th week of 
gestation (Miller et al., 2020). Spontaneous 
abortion can occur due to various reasons, 
including chromosomal abnormalities, hormonal 
imbalance, infections, immune system disorders, 
uterine or cervical abnormalities, and advanced 
maternal age, among others (Miller et al., 2020). 
Spontaneous abortion, affecting close to 30% of 
pregnancies, is a common complication, with 
recurrent pregnancy loss affecting 1 in 100 
women (Miller et al., 2020). While chromosomal 
abnormalities and thrombotic complications are 
established causes, immunologic factors, such 

as T-cell exhaustion, have also been implicated 
(Miller et al., 2020). 
 

Programmed Cell Death Protein 1 (PD-1), T Cell 
Immunoglobulin and Mucin-Domain Containing-3 
(TIM-3), and Cytotoxic T-lymphocyte-associated 
Protein 4 (CTLA-4) are critical immune 
checkpoint receptors (Catakovic et al., 2017). 
Their dysregulation can contribute to 
spontaneous abortion by disrupting immune 
tolerance during pregnancy. These markers 
maintain a balance of T helper cells (Th1/Th2) 
and regulatory T cells (Tregs), along with their 
respective cytokines, which are essential for 
pregnancy success (Li et al., 2017).   Altered 
expression of these markers can lead to T-cell 
exhaustion and recurrent miscarriages, 
underscoring their importance in maintaining the 
delicate balance of the maternal-foetal immune 
system (Li et al., 2020). 
 

This systematic review synthesised existing 
literature on TCE in spontaneous abortion and 
pregnancy, exploring its prevalence, 
mechanisms, and clinical implications to identify 
knowledge gaps and areas for future research. 
 

2. METHODOLOGY 
 

2.1 Study Design 
 

This systematic review spanned from January 
2014 to March 2024, adhering to the PRISMA 



 
 
 
 

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2020 guidelines for a comprehensive and 
transparent approach. The research process 
involved a structured identification, screening, 
eligibility, and inclusion framework conducted 
independently to minimise errors and bias. 
Studies were selected based on their relevance 
to understanding T cell exhaustion in pregnancy, 
with a focus on peer-reviewed journals. Data 
extraction encompassed T cell functionality, 
inhibitory receptor expression, cytokine profiles, 
and outcomes related to spontaneous abortion. 
Furthermore, a comprehensive review of animal 
models and clinical studies was conducted to 
gain a deeper insight into the role of T cell 
exhaustion in spontaneous abortion and 
pregnancy complications, providing a more 
complete understanding of this complex 
phenomenon. 
 

2.2 Search Strategy 
 
A systematic literature search was conducted, 
encompassing a range of databases, including 
Scopus, Google Scholar, PubMed, and Web of 

Science, to identify and synthesise the findings of 
previous studies. Applicable keywords, utilising 
Medical Subject Headings (MeSH) for PubMed, 
were combined using logical operators to 
develop a comprehensive search strategy. A 
combination of keywords from the title was used 
to construct Boolean search strings (“T cell 
exhaustion”) OR (“Immune exhaustion”) AND 
(“Spontaneous abortion”) OR (“Miscarriage”) 
AND (“Pregnancy”) in order to search and 
identify relevant studies. This methodology 
ensured a rigorous and systematic approach to 
understanding T cell exhaustion in the context of 
spontaneous abortion and pregnancy. 
 

2.3 Inclusion Criteria 
 
Available studies and data were included based 
on the following predefined criteria: (1) original 
research papers published between January 
2014 and March 2024, (2) experimental and 
Observational studies, (3) availability of full      
text, and (4) articles written and published in 
English. 

 

 
 

Fig. 1. Schematic flow diagram of the study retrieval process 



 
 
 
 

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Table 1. Summary of included articles. RSA: recurrent spontaneous abortion: RSA is defined as three or more consecutive spontaneous 
miscarriages before the 22nd week of gestation; WRSA: women with RSA; IPL: induced pregnancy loss; HC-P: healthy control pregnant; HC-NP: 

healthy control non-pregnant; decidual macrophages- Mφs; NK-cells: natural killer cells 
 

Authors; Year Population Characteristics T-Cells & Exhaustion Markers Practical implications 

Observational    

(Zych et al., 2024) 

 

  

N = 50; 20 = WRSA, 20 = 
HC-P, and 10 = HC-NP 

RSA women exhibit decreased 
expression of PD-1 and LAG-3 on 
various T cells and increased 
expression of TIGIT on NKT cells. 

• The decreased expression of PD-1 and LAG-3 may 
contribute to an enhanced inflammatory response. 

• In women with RSA, elevated TIGIT expression on NKT 
cells compensates for reduced PD-1 and LAG-3 
expression. 

(Zargar et al.,2024) N = 57; 22 = WRSA, 18 =    
recurrent implantation failure, 
and 17 = HC-P 

The mean numbers of NK cells 
(CD16+ and CD56+) and IFN-γ 
levels were significantly higher in 
the RSA 

• A significant correlation was found between the levels of 
IFN-γ and NK cells in the RPL group, indicating that 
immune dysfunction and IFN-related cytotoxicity may 
contribute to pregnancy loss. 

(Zhang et al., 2022) N=98, 17 = WRSA, 81 HC-P Decreased levels of Tim-3+ 
peripheral NK-cells and PD-1 in 
women with miscarriage 

• Lower Tim-3 levels in WRSA cases may indicate poor 
immune adaptation to pregnancy, suggesting Tim-3 
could be a marker for predicting miscarriage risk. 

(Talukdar et al., 2018)  N = 43; 26 women with 
idiopathic recurrent 
pregnancy loss (RPL) and 17 
healthy fertile controls  

Significantly elevated frequencies 
of γδ T cells correspond to 
elevated IFN-γ and TNF-α, but 
decreased IL-10, in RPLs. 

• These findings suggest a shift in γδ T cell cytokine 
profile toward a pro-inflammatory phenotype, which may 
contribute to immune dysregulation and pregnancy 
failure in women with idiopathic recurrent pregnancy 
loss. 

(Zych et al., 2021) N = 36, 24 = WRSA, 12 = 
HC-P 

Elevated PD-1 expression was 
observed on T helper (CD4+) cells 
in WRSA, while TIM-3 expression 
was decreased on T cytotoxic 
(CD8+) cells. 

• The dysregulation of the maternal immune system in 
RSA is characterised by a shift towards a Th1 cytokine 
profile and increased cytotoxicity, which may contribute 
to pregnancy loss. 

(Liu et al., 2021) N = 150; 50 = WRSA, 50 = 
HC-P and 50 = HC-NP 

 

WRSA had increased naïve CD4+ 
T cells, central memory CD4+ T 
cells, and mature NK cells, while 
terminally differentiated CD4+ T 
cells and effective memory CD4+ 
T cells were decreased. 

• Higher naïve CD4+ T cells may weaken the immune 
system, while increased central memory CD4+ T cells 
suggest altered immune responses. Elevated mature 
NK cells can cause cytotoxic effects, potentially leading 
to pregnancy loss.  Decreased terminally differentiated 
and effective memory, CD4+ T cells, indicate reduced 



 
 
 
 

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Authors; Year Population Characteristics T-Cells & Exhaustion Markers Practical implications 

 immune protection and a weaker response to 
pregnancy-related antigens. 

(Wang et al., 2020) N=65; 45 =WRSA; 20 = HC-P Increased Th1 and Th17 cells, 
and decreased regulatory Treg 
cells, were associated with a 
significant decrease in the 
expression of PD-1 on Th1 and 
Th17 cells in WRSA. 

• Increased proportions of Th1 and Th17 cells are 
associated with pro-inflammatory responses and 
decreased immune regulatory function due to altered 
PD-1/PD-L1 expression, which may have led to 
pregnancy loss. 

(Zhu et al., 2019) N=68; 33 = WRSA; 35 = HC-
P 

WRSA exhibits an activated 
immune system, characterised by 
high levels of cytotoxic NK cells 
and low levels of 
immunoregulatory IL-10+ 
CD56bright NK cells. NK cells also 
spontaneously produce a high 
amount of TGFß1. 

• This indicates a persistent inflammatory response that 
cannot be efficiently counter-regulated. This suggests 
that down-regulating the cytotoxic immune response 
and enhancing immunoregulatory mechanisms could be 
beneficial for WRSA 

(Abdolmohammadi 
Vahid et al., 2019) 

N= 100; 50 = WRSA and 50 = 
HC-P 

Treg and exhausted T cells were 
decreased, while Th17 and 
exhausted Treg cells were 
increased in WRSA. 

 

• The decrease in Treg cells and exhausted T-cells 
suggests a failure in the regulatory mechanisms that 
prevent the maternal immune system from attacking the 
foetus. 

• Increase in Th17 and exhausted Treg cells indicates a 
shift towards a pro-inflammatory immune environment. 

(Qian et al., 2018) 
N = 75; 37 = WRSA, 38 = 
HC-P 

WRSA has a higher Th17/Treg 
cell ratio at the maternal-foetal 
interface compared to women with 
normal pregnancies 

• WRSA exhibited elevated pro-inflammatory cytokine 
levels due to the skewed Th17/Treg cell ratio at the 
maternal-foetal interface, contributing to immune 
tolerance failure in WRSA. 

(Kuon et al., 2015) N = 123; 97 = WRSA; 26 = 
HC-NP 

WRSA showed higher levels of 
activated T-cells (CD3+DR+, 
CD4+DR+, and CD8+DR+) that 
were less responsive to mitogens 
than the controls. A significant 
increase in neopterin levels and 
Lower levels of CD16+CD56+ NK 
cells and CD19+ B lymphocytes 

• The chronic activation of T-cells and the deficiency in 
NK and B-cells in WRSA may contribute to the inability 
of the maternal immune system to tolerate the 
developing foetus, leading to miscarriage. 



 
 
 
 

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Authors; Year Population Characteristics T-Cells & Exhaustion Markers Practical implications 

were observed in WRSA. 

Experimental    

(Li et al., 2022) N = 135, 40 = WRSA, 86 HC-
P, 9 HC-NP 
 
 

Tim-3 expression is significantly 
decreased in WRSA, while it is 
increased in normal pregnancies. 

• Decreased Tim-3 results in the dysfunction of dMφs, 
which leads to an increase in pro-inflammatory 
cytokines and a decrease in anti-inflammatory 
cytokines, subsequently increasing foetal loss. 

(Huang et al., 2020) 
 

N = 43; 8 = WRSA, 35 = HC-
P 

The proportion of CD69+CD103+ 
resident and memory T-cells is 
significantly higher in women with 
RSA than in HC-P. 
 

• The Resident Memory T-cells expressed high levels of 
chemokine receptors such as CXCR3 and CXCR6. 
They had an enhanced capacity to produce both 
effector cytokines, TNF-α and IFN-γ, which may have 
led to pregnancy loss. 

(Liu et al., 2020) 200 specific pathogen-free 
female CBA/J mice 

Decreased PD-1 and PD-L1 
expression in the placenta and 
spleen 

• Thyroiditis in mice led to reduced PD-1 and PD-L1 
expression in the placenta and spleen, resulting in a 
decrease in Treg cells and an increase in Th17 cells at 
the maternal-foetal interface, resulting in miscarriage.  

(Luo et al., 2020) N = 12; 60 WRSA and 60  
HC-P 

Decreased expression of FOXP3 
both at the protein and mRNA 
levels and reduced frequency of 
CD4+CD25highCD127low/− 
regulatory T cells in patients with 
RSA 

• In WRSA, there is a reduction in the number and 
function of Tregs, which may lead to the immune 
system attacking the foetus, resulting in miscarriage. 

(Yu et al., 2021) N = 42; 10 = WRSA-P; 11 = 
RSA-UP; 11 = HC-P; 10 = HC 
- UP 

RSA patients exhibit increased 
CD107a expression on gdT cells, 
a higher frequency of IL-17A-
secreting Vδ2+ gdT cells, 
upregulated CCL8 expression, 
and enhanced infiltration of CD8+ 
T cells and M2 macrophages. 
Additionally, PD1 expressions on 
Vd2+ gdT cells are elevated in 
these patients. 

• Activated gdT cells, particularly those expressing 
CD107a and IL-17A, may contribute to inflammation at 
the maternal-foetal interface; these cells have an 
enhanced ability to kill other cells, potentially leading to 
RSA. 

(Wang et al., 2019) N = 37 
18 Normal pregnancies 
19 Abortion-prone model 

Decreased frequency of splenic T 
cells co-expressing CTLA-4 and 
Tim-3 in miscarriage models 

• In the Abortion Prone Model, there is a decrease in 
splenic T cells co-expressing CTLA-4 and Tim-3, which 
is linked to changes in cytokine; there is an increase in 



 
 
 
 

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Authors; Year Population Characteristics T-Cells & Exhaustion Markers Practical implications 

pro-inflammatory cytokines (e.g., TNF-α) and a 
decrease in anti-inflammatory cytokines (e.g., IL-4, IL-
10).  

(Li et al., 2017) N = 18; 10 = WRSA, HC-P = 
8 

Tim-3+ NK cells from WRSA 
produce fewer anti-inflammatory 
cytokines and have increased 
cytotoxicity compared to those 
from normal pregnancies 

• Tim-3+ NK produces more anti-inflammatory cytokines 
(TGF-β1, IL-10, IL-4) and fewer pro-inflammatory 
cytokines (TNF-α), fostering immune tolerance, and 
WRSA produces fewer anti-inflammatory cytokines, 
resulting in pregnancy loss 

 
(Xu et al., 2017) 
 
 
 
 
  

 
N=18; 9 mice were normal, 
and nine were abortion-prone 
matings in the study. 

 
Tim-3 and PD-1 pathways were 
blocked in pregnant mice.  

• TIM-3 and PD-1 regulate CD8+ T cell function to 
maintain early pregnancy in mice 

• CD8+ T cells that co-express Tim-3 and PD-1 were 
reduced in the decidua of mice with abortion-prone 
matings 

• Blocking TIM-3 and PD-1 in normal pregnant mice led to 
increased foetal resorption 

(Wang et al., 2016) 36 normal pregnant mice 
45 abortion-prone mice 
 

Decreased PD-1 and Tim-3 
expression on CD4+ T cells in 
Abortion prone Mice. 

• Blocking PD-1 and Tim-3 pathways in experimental 
models led to decreased Th2 cytokine production and 
increased foetal resorption. 

(Sun et al., 2016) 
 

N = 80; 20 = WRSA, 30 = 
HC-NP and 30 HC-P 

Tim-3 levels are lower in NK cells 
from WRSA than in normal 
pregnancies. Tim-3 is more 
abundant in dNK cells during early 
pregnancy than pNK 
cells. Blocking Tim-3 reduces 
cytokine production in dNK cells. 

• Tim-3 influences the production of cytokines like IFN-γ 
and TNF-α in dNK cells, essential for immune tolerance 
and vascular remodelling. 

• Tim-3's interaction with Galectin-9 inhibits NK cell 
cytotoxicity towards trophoblasts, preventing placental 
damage and supporting foetal development. 



 
 
 
 

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3. RESULTS AND DISCUSSION 
 

3.1 Study Identification and Retrieval 
 
Fig. 1 illustrates the step-by-step processes of 
identifying, retrieving, and selecting studies for 
this review. Our literature search yielded 23,000 
articles from Google Scholar, 12,959 from 
PubMed, and 367 from Web of Science. After 
filtering to remove duplicates and irrelevant 
studies, 50 articles qualified for a thorough full-
text evaluation. Upon further assessment, 21 of 
these studies met the predetermined inclusion 
criteria and were included in the review. 
 

4. DISCUSSION 
 
Recurrent Spontaneous Abortion (RSA) is a 
multifaceted condition where maternal immune 
dysregulation is a pivotal factor. Evidence 
consistently highlights an imbalance between 
pro-inflammatory and regulatory immune 
responses central to RSA pathophysiology. For 
example, reduced expression of immune 
checkpoints, such as PD-1 and Tim-3, on T cells 
—crucial for suppressing inflammation —has 
been observed in RSA cases, suggesting 
impaired immune tolerance at the maternal-foetal 
interface (Zych et al., 2021; Wang et al., 2020). 
Additionally, elevated levels of Th17 cells and a 
reduction in regulatory T cells (Tregs) further 
underscore a shift towards a pro-inflammatory 
immune environment that may lead to pregnancy 
loss (Vahid et al., 2018; Qian et al., 2018). 
 
Natural Killer (NK) cells also exhibit substantial 
dysregulation in RSA. Studies have documented 
increased cytotoxic NK cell activity alongside 
reduced levels of immunoregulatory subsets, a 
combination that disrupts the immune balance 
essential for successful pregnancy (Zhu et al., 
2019; Li et al., 2017). Gamma-delta T (γδT) cells, 
which produce high levels of IL-17A and express 
cytotoxic markers, contribute to this inflammatory 
milieu, further compromising pregnancy 
outcomes (Yu et al., 2021; Talukdar et al., 2018). 
 
Dysregulation of decidual macrophages (dMφs) 
and T cells is critical at the maternal-foetal 
interface. Reduced Tim-3 expression in these 
cells correlates with increased production of pro-
inflammatory cytokines and decreased 
production of anti-inflammatory cytokines, 
ultimately contributing to foetal loss (Li et al., 
2022; Xu et al., 2017). Experimental models 
underscore the significance of immune 
checkpoints, showing that blocking the Tim-3 or 

PD-1 pathways exacerbates pregnancy loss by 
inducing inflammatory and cytotoxic responses 
(Wang et al., 2016; Xu et al., 2017). 
 
The immunological environment in RSA is 
characterised by heightened inflammation and 
impaired regulatory mechanisms. Targeting 
immune checkpoints such as PD-1 and Tim-3 
offers a promising therapeutic approach to 
restore immune balance and improve pregnancy 
outcomes in RSA patients. 
 

5. FUTURE PERSPECTIVE 
 
Potential therapeutic strategies for preventing 
spontaneous abortion include targeting T-cell 
exhaustion. This can be achieved by enhancing 
Treg function, blocking inhibitory receptors on T 
cells, and modulating cytokine environments to 
restore immune balance in pregnancy. 
Diagnostic markers for T cell exhaustion, such as 
the expression of inhibitory receptors and 
cytokine profiles, could help predict and prevent 
spontaneous abortion.  Non-invasive diagnostic 
tools, such as blood tests or imaging techniques, 
could be developed to monitor immune status 
during pregnancy. 
 
Future research should focus on elucidating the 
detailed mechanisms of T cell exhaustion in 
pregnancy, identifying additional biomarkers, and 
developing targeted therapies. Collaborative 
efforts between researchers, clinicians, and 
pharmaceutical companies will be crucial for 
translating experimental findings into clinical 
practice. 
 

6. CONCLUSION 
 
Studies have identified T-cell exhaustion as a 
significant contributor to spontaneous abortion. 
This phenomenon is characterised by reduced T 
cell functionality and proliferation in women who 
have experienced spontaneous abortion. Studies 
have shown that T cell exhaustion is 
characterised by a decrease in the expression of 
stimulatory receptors and an increase in the 
expression of suppressive receptors, making it 
challenging for T cells to respond to infections. 
This highlights the critical role of T-cell 
exhaustion in spontaneous abortion. 
 
Regulatory T cells (Tregs) have been seen to 
play a vital role in maintaining immune 
homeostasis and preventing foetal rejection. 
However, women with a history of repeated 
unexplained pregnancy loss have been found to 



 
 
 
 

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have reduced Treg presence and functionality, 
which may contribute to spontaneous abortion. 

 
Furthermore, T-cell exhaustion and an overactive 
immune response have been linked to 
spontaneous abortion. Modulating the immune 
response and preventing T-cell exhaustion may 
be potential therapeutic strategies to prevent 
spontaneous abortion and promote successful 
pregnancy outcomes. Decidual natural killer cells 
(dNK) have been found to play a crucial role in 
maintaining pregnancy and preventing 
spontaneous abortion. However, an imbalance in 
dNK cells, particularly an overactivation of    
dNK1 cells, may contribute to spontaneous 
abortion. 

 
In conclusion, T cell exhaustion and immune 
modulation play a critical role in spontaneous 
abortion and recurrent pregnancy loss. Targeting 
these cell populations or their associated 
pathways may be a promising therapeutic 
strategy for preventing or treating pregnancy 
complications. Further research is needed to fully 
understand the mechanisms underlying    T cell 
exhaustion and spontaneous abortion and to 
develop practical therapeutic approaches. 

 
DISCLAIMER (ARTIFICIAL INTELLIGENCE) 

 
Author(s) hereby declare that NO generative AI 
technologies such as Large Language Models 
(ChatGPT, COPILOT, etc.) and text-to-image 
generators have been used during the writing or 
editing of this manuscript.  
 

CONSENT 
 
It is not applicable. 
 

ETHICAL APPROVAL 
 
This systematic review did not necessitate ethical 
clearance, as it relied on previously published 
studies and research works freely accessible in 
the public domain, eliminating the need for 
additional ethical oversight. 
 

COMPETING INTERESTS 
 

Authors have declared that no competing 
interests exist. 
 

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