Testosterone to Luteinizing Hormone Ratio as a Potential Predictor of Sperm Retrieval in Non-Obstructive Azoospermia Patients

Purpose@#This study assessed the outcomes of microsurgical testicular sperm extraction (mTESE) and potential preoperative predictors of sperm retrieval (SR) in patients with non-obstructive azoospermia (NOA). @*Materials and Methods@#Clinical data of 111 NOA patients who underwent mTESE was reviewed retrospectively. Baseline patient characteristics, including age, body mass index (BMI), testicular volumes, and preoperative endocrine levels, such as testosterone (T), follicle-stimulating hormone (FSH), serum-luteinizing hormone (LH), prolactin, sex hormone-binding globulin (SHBG), FSH/LH ratio along with T/LH ratio, were analyzed. After categorizing the patients into two groups based on SR success or failure, logistic regression analysis was performed to identify the preoperative predictors of successful SR. @*Results@#Sixty-eight patients had successful SR (61.3%), whereas 43 patients (38.7%) showed negative results. Failed SR group had elevated serum FSH and LH levels, whereas successful SR patients had a significantly larger testicular volume (p<0.001). Moreover, the successful group had a higher T/LH ratio (p<0.001). Multivariate logistic analysis showed that the T/LH ratio, serum FSH levels, and bilateral testicular volumes were significantly associated with successful sperm extraction. @*Conclusion@#In addition to traditional predictors, such as testicular volume and preoperative FSH levels, the T/LH ratio is a potential independent predictor of successful SR in infertile patients with NOA.

Korean Version of the Patient Perception of Study Medication Questionnaire: Translation and Linguistic Validation / 대한배뇨장애요실금학회지

Purpose@#The patient perception of study medication (PPSM) questionnaire consists of 12 questions designed to quantify patient satisfaction with the efficacy of study treatment by focusing on specific changes that patients experience during the study period. This study aimed to develop a Korean version of the PPSM questionnaire. @*Methods@#The linguistic validation process consisted of obtaining permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two independent bilingual translators translated the original version of the questionnaire, and a panel discussed and combined the 2 versions. Another independent translator performed backward translation of the reconciled version, after which 15 patients underwent the cognitive debriefing. @*Results@#The 12 questions and 4 response scales of the PPSM questionnaire were forward translated into 2 Korean versions. The terms were adjusted to conceptually equivalent expressions in Korean. After backward translation, the panel made minor changes to the forward translations for brevity and better readability. No difficulties were experienced during cognitive debriefing by 15 patients, and all items were reported to be generally easy to understand. @*Conclusions@#The Korean version of the PPSM questionnaire has been successfully translated and validated. The questionnaire is appropriate for assessing symptom satisfaction in patients that undergo benign prostatic hyperplasia pharmacotherapy.

Status of HPV vaccination among HPV-infected women aged 20–60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study / 부인종양

Objectives@#Since 2007, human papillomavirus (HPV) vaccines have been administered for the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination among HPV-infected adult women with abnormal cervical cytology before the introduction of National Immunization Program. @*Methods@#From 2010 to 2016, HPV-positive women (age, 20–60 years) with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women. @*Results@#Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women(adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29–0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13–0.96). @*Conclusion@#This study highlighted the status of HPV vaccination and the prevalence of HPV-16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

Status of HPV vaccination among HPV-infected women aged 20–60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study / 부인종양

A phase 1/2a, dose-escalation, safety and preliminary efficacy study of oral therapeutic vaccine in subjects with cervical intraepithelial neoplasia 3 / 부인종양

OBJECTIVE: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. METHODS: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. RESULTS: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. CONCLUSIONS: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02195089

Human papillomavirus genotype-specific risk in cervical carcinogenesis / 부인종양

OBJECTIVE: To evaluate the risk of genotype-specific human papillomavirus (HPV) infections for the spectrum of cervical carcinogenesis and the distribution of HPV types according to age and different cervical lesions METHODS: This study included HPV-positive women who underwent cervical biopsy at the Cheil General Hospital & Women's Healthcare Center between July 1, 2011 and December 31, 2017. HPV genotyping was conducted using a Cheil HPV DNA chip kit. RESULTS: The study sample consisted of 400 normal, 399 cervical intraepithelial neoplasia (CIN) 1, 400 CIN 2, 400 CIN 3, and 389 cervical cancer cases. HPV 16 was the most common type found with a prevalence of 9.5% in normal, 6.8% in CIN 1, 15.0% in CIN 2, 44.5% in CIN 3, and 64.3% in cervical cancer. The most common HPV types were 16, 52, 58, 53, 51, 56, 68, and 18 in all study samples. HPV 16, 31, 33, and 58 were more common in CIN 2/3 and cancer, and HPV 39, 51, 53, 56, 66, and 68 were more common in CIN 1 and normal cases (p<0.001). In CIN 3 and cervical cancer, HPV 16 was the most common type in all age groups. HPV 52 was the most common type in CIN 2 (all age groups) and in CIN 1/normal (age ≤30 years) cases. Among the high-risk HPV types, 16, 31, 33, 52, and 58 showed significant risk for high-grade disease. CONCLUSIONS: HPV 16, 31, 33, 52, and 58 showed the significant risk of high-grade disease for cervical carcinogenesis.

Impact of Cerebrovascular Disease on Survival Benefits from Local Treatment in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer

PURPOSE: Local treatment has become a treatment option for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Subgroup analyses based on a history of cerebrovascular disease (CVD) were performed to evaluate the impact thereof on overall survival (OS) after local treatment. MATERIALS AND METHODS: A retrospective analysis was performed for 879 patients with de novo mHSPC between August 2003 and November 2016. Patients were stratified according to prior CVD history and the type of initial treatment: androgen-deprivation therapy (ADT) alone versus local treatment consisting of radical prostatectomy (RP) or radiation therapy (RT) with ADT, with or without metastasis-directed therapy. The primary outcome was OS assessed by Kaplan-Meier analysis and Cox-regression models. RESULTS: Of 879 patients, 660 (75.1%) men underwent ADT alone, and 219 (24.9%) men underwent RP or RT with ADT, with or without metastasis-directed therapy. The median follow-up was 38 months. Multivariable analysis showed CVD history to be associated with a higher risk of overall mortality (p=0.001). In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher OS than men who received ADT alone (all p<0.001). However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD (p=0.324). OS was comparable between patients who received RP and RT (p=0.521). CONCLUSION: Local treatment with or without metastasis-directed therapy may provide OS advantages for mHSPC patients without a history of CVD. Further prospective studies are needed to address these important concerns.

A rare case of gastric-type mucinous adenocarcinoma in a woman with Peutz-Jeghers syndrome

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11–17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.

Currarino syndrome in an adult woman

Currarino syndrome is a hereditary disease characterized by the triad of sacral agenesis, anorectal malformation, and presacral mass. Most patients are diagnosed in childhood, and this condition rarely manifests in adulthood. In women, gynecological malformations associated with Currarino syndrome have been reported, such as bicornuate uterus, rectovaginal fistula, and septate uterus. We present a rare case of a 29-year-old woman with a suspected pelvic mass who was diagnosed with Currarino syndrome.

Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors

PURPOSE@#To determine whether systemic inflammatory response (SIR), particularly platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), has different prognostic role between patients with metastatic renal cell carcinoma (mRCC) receiving first-line tyrosine kinase inhibitors (TKI).@*MATERIALS AND METHODS@#We retrospectively reviewed 547 patients with mRCC who were diagnosed and treated with a first-line TKI between 2007 and 2015. The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). We evaluated differences in survival outcomes according to SIR and identified predictors of OS and PFS.@*RESULTS@#In synchronous mRCC, patients with a higher PLR had significantly worse OS and PFS. Moreover, a higher NLR was also associated with both worse OS and PFS in these patients. However, PLR was not associated with either OS or PFS in metachronous mRCC patients. While metachronous mRCC patients with a higher NLR had worse OS compared to those with lower NLR, there was no difference in PFS according to the status of NLR. On multivariate analysis, PLR was identified as predictive factor for OS (hazard ratio [HR], 1.55) as well as PFS (HR, 1.39) in patients with synchronous mRCC, but not in patients with metachronous mRCC. Additionally, higher NLR was also remained as predictive factor of both OS (HR, 1.83) and PFS (HR, 1.57) in patients with synchronous mRCC.@*CONCLUSIONS@#Our study indicates that simple biomarkers of SIR, particularly PLR and NLR, can be more useful predictors of survival outcomes in patients with synchronous mRCC rather than metachronous mRCC.

Risk of cervical dysplasia among human papillomavirus-infected women in Korea: a multicenter prospective study / 부인종양

OBJECTIVE: Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. METHODS: We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. RESULTS: Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p < 0.001). CONCLUSION: Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions.

The Role of B Cells in Transplantation Rejection / 대한이식학회지

B cells play a role in graft rejection via several mechanisms. Specifically, B cells produce high-affinity antibodies to alloantigens including allogeneic major histocompatibility complex (MHC) with the help of follicular helper T cells. B cells also function as antigen-presenting cells for alloreactive T cells, resulting in the activation of alloreactive T cells. Conversely, the frequency of regulatory B cells increases under inflammatory conditions and suppresses the rejection process. Here, the differential roles of the major B cell subpopulations (B-1, follicular B, marginal zone B, and regulatory B cells) involved in transplantation rejection are discussed together with their interaction with T cells.

Risk factors for cytological progression in HPV 16 infected women with ASC-US or LSIL: The Korean HPV cohort

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.

Expansion and Sub-Classification of T Cell-Dependent Antibody Responses to Encompass the Role of Innate-Like T Cells in Antibody Responses

In addition to T cell-dependent (TD) Ab responses, T cells can also regulate T cell-independent (TI) B cell responses in the absence of a specific major histocompatibility complex (MHC) class II and antigenic peptide-based interaction between T and B cells. The elucidation of T cells capable of supporting TI Ab responses is important for understanding the cellular mechanism of different types of TI Ab responses. Natural killer T (NKT) cells represent 1 type of helper T cells involved in TI Ab responses and more candidate helper T cells responsible for TI Ab responses may also include γδ T cells and recently reported B-1 helper CD4⁺ T cells. Marginal zone (MZ) B and B-1 cells, 2 major innate-like B cell subsets considered to function independently of T cells, interact with innate-like T cells. Whereas MZ B and NKT cells interact mutually for a rapid response to blood-borne infection, peritoneal memory phenotype CD49d(high)CD4⁺ T cells support natural Ab secretion by B-1 cells. Here the role of innate-like T cells in the so-called TI Ab response is discussed. To accommodate the involvement of T cells in the TI Ab responses, we suggest an expanded classification of TD Ab responses that incorporate cognate and non-cognate B cell help by innate-like T cells.

Effects of infections with five sexually transmitted pathogens on sperm quality / 대한생식의학회지

OBJECTIVE: This study investigated the prevalence of infections with human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium in the semen of Korean infertile couples and their associations with sperm quality. METHODS: Semen specimens were collected from 400 men who underwent a fertility evaluation. Infection with above five pathogens was assessed in each specimen. Sperm quality was compared in the pathogen-infected group and the non-infected group. RESULTS: The infection rates of human papillomavirus, C. trachomatis, U. urealyticum, M. hominis, and M. genitalium in the study subjects were 1.57%, 0.79%, 16.80%, 4.46%, and 1.31%, respectively. The rate of morphological normality in the U. urealyticum-infected group was significantly lower than in those not infected with U. urealyticum. In a subgroup analysis of normozoospermic samples, the semen volume and the total sperm count in the pathogen-infected group were significantly lower than in the non-infected group. CONCLUSION: Our results suggest that infection with U. urealyticum alone and any of the five sexually transmitted infections are likely to affect sperm morphology and semen volume, respectively.

Clinical Features of Recurrent Intermittent Exotropia after Reoperation for Intermittent Exotropia

PURPOSE: We reviewed the clinical features of intermittent exotropic patients who experienced recurrence after reoperation for intermittent exotropia, and identified the risk factors and prognoses. METHODS: The incidences, risk factors, treatment modalities, and prognoses of patients with recurrent exotropia were analyzed in 39 patients who underwent reoperation due to a relapse of exotropia after the first intermittent exotropia. RESULTS: Among 39 patients, 24 (61.5%) had recurrent intermittent exotropia and 15 patients had no recurrence with intermittent exotropia. There was no difference in the recurrence of intermittent exotropia with age, deviation, refraction, anisometropia, outward discrepancy, and the vertical deviation before the reoperation. However, when the first operation was performed with bilateral lateral rectus recession and the reoperation was performed with bilateral medial rectus resection or unilateral medial rectus resection, intermittent exotropia tended to recur more than when the first operation was performed with one eye with lateral rectus recession and medial rectus resection, followed by reoperation with the other lateral rectus recession and medial rectus resection (p 10 prism diopters (p < 0.05). CONCLUSIONS: The factors affecting recurrence after intermittent exotropia surgery involve surgical factors such as the surgical method and the postoperative overcorrection.

Serosal Cavities Contain Two Populations of Innate-like integrin α4highCD4+ T Cells, Integrin α4β1+α6β1+α4β7− and α4β1+α6β1−α4β7+ Cells

We previously reported peritoneal innate-like integrin α4 (CD49d)highCD4+ T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4highCD4+ T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4highCD4+ T cells to integrin α4lowCD4+ T cells than peritoneal cavity, but the pleural integrin α4highCD4+ T cells have the same characteristics of the peritoneal integrin α4highCD4+ T cells. Most of integrin α4highCD4+ T cells were integrin β1highβ7−, but a minor population of integrin α4highCD4+ T cells was integrin β1+β7+. Interestingly, the integrin α4highβ1highβ7− CD4+ T cells expressed high levels of integrin α4β1 and α6β1, whereas integrin α4highβ1+β7+ CD4+ T cells expressed high levels of integrin α4β1 and α4β7, suggesting an alternative expression of integrin α6β1 or α4β7 in combination with α4β1 in respective major and minor populations of integrin α4highCD4+ T cells. The minor population, integrin α4highβ1+β7+ CD4+ T cells, were different from the integrin α4highβ1highβ7− CD4+ T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin α4highβ1 highβ7− CD4+ T cells. In summary, the innate-like integrin α4highCD4+ T cells could be divided into 2 populations, integrin α4β1+α6β1+α4β7− and α4β1+α6β1−α4β7+ cells. The functional significance of serosal integrin α4β7+ CD4+ T cells needed to be investigated especially in view of mucosal immunity.