Effects of estrogen on CD4^+ CD25^+ regulatory T cell in peripheral blood during pregnancy

Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.

An Association between Immunosenescence and CD4^+CD25^+ Regulatory T Cells: A Systematic Review

Objective Age-related increment of the prevalence of CD4^＋CD25^＋ regulatory T （Treg） cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8＋ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^＋CD25^＋ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease （AD） and Parkinson disease （PD）. The impaired condition of CD4＋ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.

Analysis of CD4^+CD25^+ Regulatory T Cells and Foxp3 mRNA in the Peripheral Blood of Patients with Asthma

The changes of CD4^＋CD25^＋ regulatory T cells （CD4^＋CD25^＋ Treg） and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） from patients with asthma were investigated in order to elucidate the possible roles of CD4^＋CD25^＋ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls （normal control group） and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups （P〈0.05）. Although the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them （P〉0.05）. As compared with persistent group, exacerbation group had lower CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA （P〈0.05）. It was indicated that the decrease of CD4^＋CD25^＋ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.

Changes of CD4^+CD25^+ Regulatory T Cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin

The function of CD4＋CD25＋ regulatory T lymphocytes （Treg） in patients with acute coronary syndrome （ACS） and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups： group C receiving conventional therapy （n=24）, and group C＋A receiving conventional therapy＋atorvastatin （10 mg/day, n=24）. T lymphocytes from ACS patients （before and 2 weeks after the treatment） or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction （MLR）. ELISA was used to measure the serum levels of cytokines （IL-10, TGF-β1 and IFN-γ） before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly （P〈0.01）, the inhibitory ability of Treg on the T lymphocytes proliferation was reduced （P〈0.01）, IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.

Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.

Isolation and identification of CD4^+CD25^+ regulatory T cells in rat

Objective： To establish a stable and high efficient method for collection of CD4^＋CD25^＋ regulatory T cells from rats in vitro. Methods： CD4^＋CD25^＋ regulatory T cells were isolated from the rat splenic cells through two steps by magic cell sorting （MACS） system. The first step was negative selection of CD4^＋T cells by cocktail antibodies and anti-IgG magic microbeads, and the second step was positive selection of CD25^＋T cells by anti-CD25 PE and anti-PE magic microbeads. The purity and viability of separated cells were measured by flow cytometry （FACS） and Trypan blue staining. The suppressive ability of seperated cells on the proliferation of CD4^＋CD25^- T cells was assessed by cell proliferation assay. Results： The purity of negatively enriched CD4^＋ T cells was 79%-87% （83.6%±2.5% ） , and the purity of positively enriched CD4^＋CD25^＋ T cells was 86%- 93% （ 90.2±1.8% ） with the viability of 92%～95% （92.8% ± 3.4% ）. The enriched cells significantly suppressed the proliferation of CD4^＋CD25^- T cells in mixed lymphocyte culture （P 〈 0.05）. Conclusion： An effective method can be established for enrichment of CD4^＋CD25^＋ regulatory T cells in two steps by MACS, with satisfied cell purity, viability and function.

CD4^+CD25^(high) Regulatory Cells in Peripheral Blood of NSCLC Patients

The proportion and changes of CD4^＋CD25^high regulatory T cells （Trs） in peripheral blood of non-small cell lung cancer （NSCLC） patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets （CD3^＋, CD4^＋ and CD8^＋） and CD4^＋CD25^high Tr cells. The results showed that the proportion of CD4^＋CD25^high Tr cells in NSCLC group was significantly higher than in control group [（4.36 ±2.07） % vs （2.04±1.03） %, P〈0.01]. The proportion of CD4^＋CD25^ high Tr cells in late stage was higher than that in early stage [stages Ⅰ ＋Ⅱ （2.264±0.6） %; stage Ⅲ（3.284± 1.38） %; stage IV （6.06 4±4.08） %] （P〈0.05）. Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4^＋CD25^high Tr cells in peripheral blood was worse （P=0.0026）. In conclusion, the relative increase in CD4^＋CD25^high Tr cells in peripheral blood may be related to im- munosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4^＋CD25^high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4^＋CD25^high Tr cell therapy to treat NSCLC patients may be an effective strategy.

CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients

AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Biological features of intrahepatic CD4^(+)CD25^(+)T cells in the naturally tolerance of rat liver transplantation

The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplan-tation was performed in two allogeneic rat strain combina-tions,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients[Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DA-to-DA].The proportion of intrahepatic CD4^(+)CD25^(+)T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4^(+)CD25^(+)T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4^(+)CD25^(-)T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The pro-portion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tole-rance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4^(+)CD25^(+)T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4^(+)CD25^(+)Tcells sorted by MACS was 86%–93%.The CD4^(+)CD25^(+)T cells could specifically express the Foxp3 gene compared with CD4^(+)CD25^(-)T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4^(+)CD25^(+)T cells more obviously than the syngegnic spleen cells.CD4^(+)CD25^(+)Tr cells could suppress the proliferation of CD4^(+)CD25^(-)T cells,but the inhibition was reversed by exo-genous IL-2(200 U/mL).The CD4^(+)CD25^(+)T regulatory cells specifically express the Foxp3 gene,which may play animpor-tant role in the induction of liver transplantation tolerance by suppressing the reaction of effective T cells.

Berberine improves central memory formation of CD8^(+)T cells:Implications for design of natural product-based vaccines

Berberine(BBR)as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities.However,it is unknown if BBR can be applied without abrogating the efforts of vaccination.Here we show that priming of CD8^(+)T cells in the presence of BBR lead to improved central memory formation(Tcm)with substantially reduced effector proliferation,primarily orchestrated through activation of AMPK and Stat5.Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naIve recipients.Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy,suggesting appreciable benefits from using BBR in vaccination.Thus,our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.

Alterations of peripheral CD4^(+)CD25^(+)Foxp3^(+)T regulatory cells in mice with STZ-induced diabetes

Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients.CD4^(+)CD25^(+)T regulatory cells(Tregs)play pivotal roles in controlling immune homeostasis,immunity and tolerance.The effect of hyperglycemia on CD4^(+)CD25^(+)Tregs has not yet been addressed.Here we used streptozotocin(STZ)-induced diabetic mice to study the effects of long-term hyperglycemia on CD4^(+)CD25^(+)Tregs in vivo.Four months after the onset of diabetes,the frequency of CD4^(+)CD25^(+)Foxp3^(+)T regulatory cells was significantly elevated in the spleen,peripheral blood lymphocytes(PBLs),peripheral lymph nodes(pLNs)and mesenteric LNs(mLNs).CD4^(+)CD25^(+)Tregs obtained from mice with diabetes displayed defective immunosuppressive functions and an activated/memory phenotype.Insulin administration rescued these changes in the CD4^(+)CD25^(+)Tregs of diabetic mice.The percentage of thymic CD4^(+)CD25^(+)naturally occurring Tregs(nTregs)and peripheral CD41Helios1Foxp31 nTregs were markedly enhanced in diabetic mice,indicating that thymic output contributed to the increased frequency of peripheral CD4^(+)CD25^(+)Tregs in diabetic mice.In an in vitro assay in which Tregs were induced fromCD4^(+)CD25^(+)T cells by transforming growth factor(TGF)-b,high glucose enhanced the efficiency of CD4^(+)CD25^(+)Foxp3^(+)T inducible Tregs(iTregs)induction.In addition,CD4^(+)CD25^(+)T cells from diabetic mice were more susceptible to CD4^(+)CD25^(+)Foxp3^(+)TiTreg differentiation than those cells from control mice.These data,together with the enhanced frequency of CD4^(+)CD25^(+)Foxp3^(+)T iTregs in the periphery of mice with diabetes,indicate that enhanced CD4^(+)CD25^(+)Foxp3^(+)T iTreg induction also contributes to a peripheral increase in CD4^(+)CD25^(+)Tregs in diabetic mice.Our data show that hyperglycemia may alter the frequency of CD4^(+)CD25^(+)Foxp3^(+)T Tregs in mice,which may result in late-state immune dysfunction in patients with diabetes.

CD4^＋CD25^＋ regulatory T lymphocytes in tuberculous pleural effusion

Background Active suppression by CD4^＋CD25^＋ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens. This study was conducted to analyze whether the CD4^＋CD25^＋ regulatory T cells exist and function normally in tuberculous pleural effusion. Methods The percentages of CD4^＋CD25^＋ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry. The expression of forkhead transcription factor Foxp3 was also examined. CD4^＋CD25^＋ and CD4^＋CD25^-T cells from pleural effusion and blood were isolated, and were cultured to observe the effects of CD4^＋CD25^＋ T cells on proliferation response of CD4^＋CD25^- T cells in vitro. Results There were increased numbers of CD4^＋CD25^＋ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects, and these cells demonstrated a constitutive high-level expression of Foxp3. Moreover, CD4^＋CD25^＋ T cells mediated potent inhibition of proliferation response of CD4^＋CD25^- T cells. Conclusion The increased CD4^＋CD25^＋ T cells in tuberculous pleural effusion express a high level of Foxp3 transcription factor, while potently suppressing the proliferation of CD4^＋CD25^- T cells.

CD4^＋CD25^＋调节性T淋巴细胞与卵巢上皮性癌关系的研究进展

卵巢上皮性癌（卵巢癌）的治疗方法包括手术结合化疗或放疗，但以上方法均未能使晚期卵巢癌患者约30％的5年生存率得以改善，使卵巢癌成为妇科肿瘤中的治疗难点，促使我们寻找新的治疗手段。近年来，免疫治疗成为肿瘤治疗的新辅助方法，显示了一定的治疗效果，其中CD4^＋CD25^＋去调节性T淋巴细胞（regulatory T cells，Tr细胞）成为研究热点，并逐渐从基础研究过渡到临床研究，本文就其在卵巢癌中的研究进展进行综述。

CD4^＋CD25^＋调节性T细胞在自身免疫性肝病中的研究进展

调节性T细胞（regulatory T cells，Tregs）是一组天然存在或诱导成熟T细胞而产生的具有调节功能的T细胞亚群，CD4^＋CD25^＋调节性T细胞足Tregs中主要的亚群。1995年Sakaguchi等首次报道后，有关CD4^＋CD25^＋调常性T细胞的研究已涉及到各个领域，本文就CD4^＋CD25^＋调节性T细胞在自身免疫性肝病中的研究进展作一综述。

CD4^＋CD25^＋调节性T细胞对肝癌特异性细胞毒性T淋巴细胞杀伤活性的影响

CD4^＋CD25^＋调节性T细胞（regulatory T cells，Treg）是体内最主要的免疫调节细胞，研究发现多种肿瘤患者的外周血及肿瘤局部均有Treg的比例增高，提示Treg在肿瘤的发生发展过程中可能起重要的作用。树突状细胞（DC）是目前已知的体内最强的专职抗原呈递细胞，可在体内、外向T淋巴细胞呈递抗原，并诱发细胞毒性T淋巴细胞（CTL）反应。本实验用H22小鼠肝癌细胞（H22细胞）全细胞抗原致敏DC（抗原致敏DC），

CD4^＋CD25^＋调节性T细胞—免疫治疗新策略

1995年日本学者Sakaguchi等^[1]首次证实外周血中CD4^＋T细胞中5％-10％的CD4^＋CD25^＋T细胞具有免疫抑制功能，它们能预防和阻止自身免疫病的发生发展，这群细胞被定义为CD4^＋CD25^＋调节性T细胞（regulatory T cells，Treg）。近十多年对Treg在自身免疫病发病中的作用及机制进行了深入研究，

An altered CD8^(+) T cell epitope of insulin prevents type 1 diabetes in humanized NOD mice

Autoreactive CD8^(+)T cells,which play an indispensable role inβcell destruction,represent an emerging target for the prevention of type 1 diabetes(T1D).Altered peptide ligands(APLs)can efficiently induce antigen-specific T cells anergy,apoptosis or shifts in the immune response.Here,we found that HLA-A*0201-restricted CD8^(+)T cell responses against a primaryβ-cell autoantigen insulin epitope InsB15–14 were present in both NOD.β2m null.HHD NOD mice and T1D patients.We generated several APL candidates for InsB15–14 by residue substitution at the p6 position.Only H6F exhibited an inhibitory effect on mInsB1_(5–14)-specific CD8^(+)T cell responses in vitro.H6F treatment significantly reduced the T1D incidence,which was accompanied by diminished autoreactive CD8^(+)T cell responses to mInsB15-14,inhibited infiltration of CD8^(+)and CD4^(+)T cells in the pancreas and reduced pro-inflammatory cytokine production in pancreatic and splenic T cells in NOD.β2m^(null).HHD mice.Mechanistically,H6F treatment significantly augmented a tiny portion of CD8^(+)CD25^(+)Foxp3^(+)T cells in the spleen and especially in the pancreas.This subset exhibited typical Treg phenotypes and required peptide-specific restimulation to exert immunosuppressive activity.Therefore,this APL H6F may be a promising candidate with potential clinical application value for antigen-specific prevention of T1D.

Enhancement of antitumor immunity by low-dose total body irradiation is associated with selectively decreasing the proportion and number of T regulatory cells

Low-dose total body irradiation （LTBI） is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4^＋CD25^＋Foxp3^＋ regulatory T cells are markedly decreased in naive mice following treatment with LTBI. On the contrary, the CD4^＋CD44^＋/CD8^＋CD44^＋ effector-memory T cells are greatly increased. Importantly, naive mice treated with dendritic cell-gp100 tumor vaccines under LTBI induced an enhancement of antigen-specific proliferation and cytotoxicity as well as interferon-γ, （IFN-γ） secretion against FIO melanoma tumor challenge, compared to treatment with either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a reduced tumor burden and prolonged mouse survival. Our data demonstrate that LTBI＇s enhancement of antitumor immunity was mainly associated with selectively decreasing the proportion and number of T regulatory cells, implying the potential application of the combination of LTBI and a tumor vaccine in antitumor therapy.