• 생명과학회지
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• 제25권6호
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• pp.686-692
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• 2015

암조직에 대한 면역반응은 종양의 성장을 억제하거나 유도한다. Foxp3 양성 T 림프구는 종양에 대한 면역억제 반응을 유도하여 종양의 성장을 유도하는 반면 CD8 양성 T 림프구는 종양의 성장을 억제한다. 본 연구에서는 피부에서 발생한 편평세포암종, 편평세포 암종의 전암병변인 광선각화증과 보웬병 그리고 기저세포암종 조직에 면역조직화학염색을 시행하여 CD8 양성 T 림프구 및 Foxp3 양성 T 림프구의 분포 그리고 두 종류의 림프구의 비(CD8/Foxp3)를 조사하여 다음과 같은 결과를 얻었다. CD8 양성 T 림프구와 Foxp3 양성 T 림프구는 보웬병과 평평세포암종의 침습부위에서 광선각화증과 기저세포암종의 침습부위에 비하여 더 많이 침윤하였으며 CD8/Foxp3는 보웬병에서 광선각화증과 기저세포암종의 침습부위에 비하여 낮았다. CD8 양성 T 림프구와 Foxp3 양성 T 림프구의 침윤 정도 및 CD8/Foxp3는 보웬병과 편평세포암종의 침습부위에서 유의한 차이가 없었다. 기저세포암종과 편평세포암종에서 CD8 양성 T 림프구와 Foxp3 양성 T 림프구는 침습부위에서 종양의 중심부위에 비하여 더 많이 침윤하였다. 이러한 결과로 보아 편평세포종양과 기저세포암종은 서로 다른 면역반응을 보이며 종양내에서도 부위에 따라 상이한 면역반응을 보인다고 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.867-872
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• 2012

Background: $FOXP3^+$ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. Design: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect $FOXP3^+$ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. Results: The presence of $FOXP3^+$ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between $FOXP3^+$ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between $FOXP3^+$ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. Conclusions: In this study, a positive correlation between the presence of $FOXP3^+$ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

• BLOOD RESEARCH
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• 제53권4호
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• pp.294-298
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• 2018

Background Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert $CD4^+CD25^-$ conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. Methods Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. Results Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). Conclusion Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

• IMMUNE NETWORK
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• 제11권6호
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• pp.336-341
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• 2011

T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.

• IMMUNE NETWORK
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• 제23권5호
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• pp.37.1-37.11
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• 2023

Forkhead box P3-positive (Foxp3⁺)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

• Clinical and Experimental Reproductive Medicine
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• 제44권4호
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• pp.214-223
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• 2017

Objective: In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. Methods: This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. Results: Before seminal plasma exposure, the expression levels of T-bet (p< 0.007), $interferon-{\gamma}$ (p= 0.013), and tumor necrosis factor $(TNF)-{\alpha}$ (p= 0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p< 0.001), Foxp3 (p= 0.001), and interleukin (IL)-35 (p< 0.003) were lower. After seminal exposure, the expression of T-bet (p= 0.02), Rorc (p< 0.001), $TNF-{\alpha}$ (p= 0.001), Foxp3 (p= 0.02), and $interferon-{\gamma}$ (p= 0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p= 0.02), Rorc (p< 0.001), IL-23 (p= 0.04), IL-17 (p= 0.02), IL-6 (p< 0.001), transforming growth $factor-{\beta}$ (p= 0.01), and IL-35 (p< 0.001) increased in the successful IVF group. Conclusion: In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.