High numbers of T cells in gingiva from patients with human immunodeficiency virus (HIV) infection

A quantitative, immunohistologic evaluation of CD3⁺, CD4⁺and CD8⁺ cells was carried out on gingival biopsies from 25 HIV-infected persons with gingivitis or periodontitis and 13 HIV-seronegative persons with periodontitis. CD3⁺ T cells were found in all biopsies. CD8⁺ cells were significantly more numerous and the CD4⁺/CD8⁺ ratio was significantly decreased in the gingival connective tissue of the HIV⁺ patients (P < 0.05). The number of CD4⁺ lymphocytes subjacent to the pocket epithelium was moderately lower in the HIVH patients as compared to the HIV⁺ patients (P < 0.05). HIV⁺ patients with a history of necrotizing periodontal disease had fewer CD4⁺ cells subjacent to the oral gingival epithelium than patients without such disease (P < 0.05). The general HIV-related changes in T lymphocyte numbers were therefore reflected in inflamed gingival tissues. HIV⁺ patients had, however, significantly higher CD4⁺/CD8⁺ ratios in gingiva than in peripheral blood (P < 0.05), indicating that CD4⁺ T cells are actively recruited to gingiva, even in cases of extreme CD4⁺ T lymphocytopenia.     

4-1BB、CD8在口腔扁平苔藓组织中的表达研究

目的 检测共刺激信号4-1BB及CD8在口腔扁平苔藓(oral lichen planus,OLP)组织中的表达,探讨OLP病损中4-1BB介导CD8⁺ T细胞免疫应答的潜在机制。方法 选取31例OLP患者(糜烂型15例、非糜烂型16例),15例健康成人(对照组)为研究对象,收集其临床及病理资料,采用免疫组织化学法检测局部组织中4-1BB、CD8的表达情况。结果 OLP患者局部组织中4-1BB及CD8的表达高于对照组(P<0.05),且两者表达呈正相关(r=0.389,P<0.05),糜烂型OLP患者中CD8、4-1BB表达高于非糜烂型(P<0.05)。在OLP不同的临床亚组中,VAS评分、REU评分及基底细胞损伤程度均表现出差异(P<0.05)。Spearman相关性分析结果显示,CD8与基底细胞损伤程度呈正比(P<0.05),CD8、4-1BB分别与VAS评分、REU评分存在正相关性(P<0.05)。结论 OLP患者局部组织中4-1BB表达升高,其与疾病活动进展程度呈正相关,4-1BB可能通过调控CD8⁺ T细胞参与OLP的发生发展。     

Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus

This study has addressed the question of whether there is selective recruitment and distribution of intra-epithelial leucocytes in lesions of oral lichen planus (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood of patients and controls using flow cytometry and double immunofluorescence, and the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression with T-lymphocyte and Langerhans cell (LC) distribution was examined. The circulating 'memory'subset (CD45RO⁺) of T-helper cells (CD4⁺) was increased from 49.1% in controls to 65.7% in patients ( P = 0.005), while the 'naive'subset (CD45RA⁺), which was absent from control epithelium, comprised 24% of helper cells in OLP ( P =0.037) and all T-cell and LC counts were significantly raised in ICAM-1-expressing areas of epithelium. These data demonstrate changes in intra-epithelial T-lymphocyte and LC populations compared with normal oral mucosa and suggest there is selective recruitment in OLP. In addition, Keratinocyte ICAM-1 expression does appear to be associated with accumulation of infiltrating T lymphocytes and LC.     

FOXP3+ T regulatory cells in lesions of oral lichen planus correlated with disease activity

Objective:  The aim of this study was to determine the correlation between the number of FOXP3⁺ T cell in lesions and the disease activity of patients with oral lichen planus (OLP).
Materials and Methods:  The expression of FOXP3 was investigated using immunohistochemical staining and real-time RT-PCR in 23 OLP lesions and 12 controls. Changes of FOXP3⁺ Treg in peripheral blood from three patients' pre and post-treatment were assessed using flow cytometry.
Results:  Few FOXP3⁺ cells were detected in controls, but an increased number of FOXP3⁺ cells were observed in lesions ( n  = 20, 40.99 ± 24.68 cells per high-power field – hpf). Furthermore, the frequency of FOXP3⁺ Treg in reticular OLP ( n  = 7, 63.6 ± 23.2 cells per hpf) was significantly higher than that in erythematous/erosive OLP ( n  = 13, 28.8 ± 16.8 cells per hpf, P  = 0.001). In addition, negative correlation was found between the number of FOXP3⁺ Treg and disease activity (correlation oefficient = −0.557, P  = 0.013). The proportion of FOXP3⁺ Treg showed remarkable increase in peripheral blood from patients after treatment (1.39 ± 0.71% vs 4.91 ± 1.59%).
Conclusions:  These data indicated that FOXP3⁺ Treg were involved in the pathogenesis of OLP and correlated with disease's subtype and activity.     

Systemic treatment of anti-CD4+CD25+ T cell monoclonal antibody exacerbates sialoadenitis in submandibular glands during the early life in lupus-prone female NZB × NZWF1 mice

Background:  The maintenance mechanisms of peripheral tolerance by CD4⁺CD25⁺ T cells before the development of sialoadenitis in secondary Sjögren's syndrome (sSS) are not well understood. The aim of the present study is to examine the effect of reduction of CD4⁺CD25⁺ T cells on the development of sialoadenitis during the early life in female NZB × NZWF₁ (B/WF₁) mice, a model for human sSS.
Methods:  Female B/WF₁ mice at 3 days after birth were treated with either anti-mouse CD4⁺CD25⁺ T cells rat IgG₁ monoclonal antibody (mAb) or Rat IgG₁(control). At 25 weeks of age, autoantibodies against nucleus and cytoplasm of ductal epithelial and myoepithelial cells, and histpathology of submandibular glands were examined in the mAb-treated and control groups. Also the development of anti-Ro/SS-A antibodies was examined until 25 weeks of age in both groups.
Results:  The mAb-treated group showed severe lesions with the development of autoantibodies compared to the control group.
Conclusions:  The present results suggest that peripheral CD4⁺CD25⁺ T cells may, at least in part, contribute to down-regulate the development of sialoadenitis in submandibular glands of lupus-prone female B/WF₁ mice during their early life.     

Increased number of CD25+ FoxP3+ regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining

Background:  The role of tumor-infiltrating regulatory T cells (Treg) compromising antitumor effects of immune cells in oral squamous cell carcinoma (OSCC) is largely unknown.
Purpose:  The presence of CD25⁺ FoxP3⁺ Treg as well as of CD3⁺ FoxP3⁺ and of CD8⁺ FoxP3⁺ tumor-infiltrating lymphocytes (TIL) was verified in OSCC and compared with non-cancerous lymphoepithelial tissue.
Method:  Three double stainings (CD3/FoxP3, CD8/FoxP3 and CD25/FoxP3) were performed on tissue sections of 15 OSCC and compared with 15 human tonsils.
Results:  OSCC biopsy samples provide evidence for a strong infiltration of TIL, in particular, naturally occurring CD25⁺ FoxP3⁺ Treg. Whereas a comparison of OSCC and control tissue did not show significant changes in the number of CD3⁺ FoxP3⁺ TIL and of CD8⁺ FoxP3⁺ TIL, a significantly higher frequency of CD25⁺ FoxP3⁺ TIL (Treg) could be observed in OSCC ( P  < 0.001, two-sided t -test). Given the small number of specimens, a significant correlation with tumor stage could not be verified.
Conclusion:  Chromogenic double staining of CD4/FoxP3 is a promising tool for the detection of Treg in paraffin-embedded tissue of OSCC.     

Oral candidiasis and immune status of HIV-infected patients

A total of 84 HIV-infeted homosexual men having either normal oral mucosa (NOM). erythematous candidiasis (EC) or pseudomembranous candidiasis (PsC) were included in the study. The patients were evaluated by median number of peripheral CD4⁺ cells, CD8⁺ cells and by lymphocyte function assessed by poke-weed mitogen test. There was a significant difference between CD4⁺ counts among patients with the two subtypes of candidiasis (95% CI of median difference: 10 240/mm³; P =0.03). but not for pokeweed mitogen response. Survival analysis showed that after 2 y there was no significant difference in development of AIDS between patients with EC and PsC ( P = 0.29). If patients with both types of oral candidiasis were pooled and compared with patients with NOM. a significant difference in development of AIDS was found ( P = 0.04). It is concluded that HIV-infected patients with oral candidiasis of any subtype (EC or PsC) arc significantly more immune suppressed and show a faster development of AIDS than HIV-infected patients with NOM. However, in this cohort. EC and PsC are of equal importance as predictors for immune suppression and AIDS development.     

Oral ulcers in HIV-positive Peruvian patients: an immunohistochemical and in situ hybridization study

Background:  This study describes the histopathological, immunohistochemical (IHC) and in situ hybridization (ISH) data of 25 cases of oral ulcers in HIV-positive patients, with clinical and microscopical features similar to ulcers not otherwise specified (NOS)/necrotizing ulcerative stomatitis (NUS).
Methods:  Sex, age and clinical history were obtained from the clinical records. Histological analysis for H&E, Gomori–Grocott and Ziehl–Neelsen stains, IHC analysis to detect infectious agents and to characterize inflammatory cellular infiltrate, and ISH for cytomegalovirus (CMV) and EBER1/2 were performed.
Results:  Twenty-one patients were men and four were women (mean age of 34.6 years). The tongue was preferentially affected. Microscopically, the lesions showed extensive necrosis, leukocytoclasia, vasculitis with luminal fibrin clots and an intense inflammatory cellular infiltrate predominated by CD68⁺ atypical large cells, normal-sized and crescent-shaped nuclei macrophages, interspersed by CD8⁺ T lymphocytes. Mast cells were also observed in all samples studied. CD4⁺ T lymphocytes, CD20⁺ B lymphocytes and VS38c⁺ plasma cells were practically absent. CMV and EBER1/2 were identified in scarce cells of 3 and 16 of 25 cases respectively.
Conclusion:  These results show that CD68⁺ macrophages, followed by CD8⁺ T lymphocytes, were the predominant inflammatory cells, indicating they are relevant to the pathogenesis of the ulcers, possibly reflecting an abnormal immune response in the oral mucosa. The clinicopathological and immunoprofile features of the present cases are similar to NOS ulcers/NUS in HIV-positive patients.     

The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis

Objective.   The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis.
Material and methods.   Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4⁺ and CD8⁺ T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4⁺/CD8⁺ ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t -test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements.
Results.   The CD4⁺/CD8 ratio in gingival tissues obtained from test group was significantly higher ( P <  0.05) than that found in the gingival tissue obtained from control group. We found that the CD4⁺ and CD8⁺ lymphocyte counts continued to increase significantly ( P <  0.001) and the CD4⁺/CD8⁺ ratio continued to drop significantly ( P <  0.05) after treatment in test group.
Conclusions.   T lymphocytes could play a significant role in the pathobiology of puberty gingivitis     

T细胞免疫和细胞凋亡在口腔扁平苔藓发病中的作用

目的通过探讨口腔扁平苔藓（OLP）中细胞凋亡情况及CD4＋、CD8＋T细胞和CD4/CD8比例的变化分析细胞免疫与细胞凋亡的关系,进一步了解OLP的发病机制。方法应用免疫组化SP法检测27例OLP组织中CD4＋、CD8＋T细胞的表达水平,并用原位末端转移酶标记法（TUNEL）定位检测17例OLP中细胞凋亡情况。结果OLP组固有层中CD4＋、CD8＋T细胞明显高于对照组（P＜0.05）,CD4/CD8值降低。OLP组中上皮内细胞凋亡指数高于对照组,固有层淋巴细胞凋亡指数明显低于对照组。结论OLP组固有层中CD4＋、CD8＋T细胞浸润的增加、CD4/CD8比值的变化及OLP中上皮细胞和固有层淋巴细胞凋亡异常,说明细胞免疫功能紊乱和细胞凋亡异常在OLP发病中起重要作用。     

Inflammatory cell infiltrate associated with primary and transplanted tumours in an inbred model of oral carcinogenesis

This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately- to well-differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5–6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45⁺, Ia⁺) and contained smaller numbers of CD8⁺ cells (NK cells, cytotoxic/suppressor T cells), CD5⁺ cells (T cells) and CD25⁺ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour-derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour-derived cell lines were tumorigenic in athymic ( nu/nu ) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non-tumorigenic in athymic mice. Three of four malignant cell lines formed well-differentiated tumours in syngeneic F344 rats; the tumours regressed after 10–14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5^-, CD8⁺) in the inflammatory cell infiltrate compared with that associated with primary tumours (p<0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell-mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.     

Immunoelectron microscopic study of distribution of T cell subsets in oral lichen planus

Abstract – Monoclonal anti-CD4, anti-CD8, and anti-GD18 antibodies were applied in avidinbiotin-peroxidase complex staining using a pre-embedding immunoelectron microscopy technique. Although most of the local T cells in situ were of CD4⁺ subtype, local CD8⁺ cells generally had a lower nucleus/cytoplasm ratio and contained more cell organelles than CD4⁺ cells. This suggests a local activation of CD8⁺ subpopulation, rather than activation of the numerically predominant CD4⁺ cells. Topographical analysis disclosed that all lymphocytes, regardless of location, were CD18⁺ and that most of the CD8 ⁺ cells were located subbasally and intraepithelially, whereas CD4⁺ cells often occurred in small clusters deeper down in the subepithelial lymphocyte-rich band. Furthermore, CD8⁺ cells were often in close contact with macrophages, whereas CD4⁺ cells were in some instances in direct contact with plasma cells. This indicates that CD4⁺ cells may be involved in T cell-dependent B cell-mediated immunoglobulin synthesis, whereas CD8⁺ cytotoxic lymphocytes and tissue macrophages may be involved in the local pathogenetic process leading to basement membrane alterations.     

OLP外周血中CD4＋CD25＋T细胞体外增殖及对CD4＋CD25-T细胞增殖的影响

目的：通过检测口腔扁平苔藓（OLP）患者外周血中CD4＋CD25＋T细胞的体外增殖及对CD4＋CD25＋T细胞增殖的影响,探讨调节性T细胞对OLP特异性细胞免疫的调节作用及其在该病发生中的意义。方法：通过免疫磁珠分离系统（MACS）分选OLP患者和健康志愿者外周血单个核细胞（peripheral blood mononuclear cell,PBMC）中的调节性T细胞（regulatory Tcell,Treg）和效应性T细胞（responder Tcell,Tresp）,采用流式细胞术检测其纯度、3H--脱氧胸腺嘧啶苷方法检测CD4＋CD25＋T细胞对CD4＋CD25＋T细胞增殖的影响,比较OLP患者和健康志愿者体内Treg细胞功能。结果：分选后健康对照组及OLP患者外周血中CD4＋CD25＋T细胞纯度均高于85％。无论是健康对照还是OLP患者的CD4＋CD25-T细胞均明显抑制CD4＋CD25-T细胞的增殖。与健康对照组相比,OLP组CD4＋CD25＋T细胞对CD4＋CD25-T细胞增殖的抑制作用显著降低旧〈0．01）。结论：调节性T细胞可能通过抑制OLP特异性细胞免疫应答促进疾病的发生发展。     

Increased levels of circulating endothelial progenitor cells in subjects with moderate to severe chronic periodontitis

Aim: Emerging evidence shows that periodontal disease is associated with endothelial dysfunction. The purpose of this study was to determine the association between chronic periodontitis (CP) and circulating endothelial progenitor cells (EPC).
Materials and Methods: Eighty-six non-smoking subjects (36 males and 50 females, aged 35–80 years) were recruited, including 23 subjects with no or mild CP and 63 subjects with moderate to severe CP. The levels of circulating EPC were quantitatively determined by fluorescence-activated cell analysis, including CD34⁺/kinase insert domain-containing receptor (KDR)⁺ (more mature EPC) and CD133⁺/KDR⁺ (less mature EPC). Periodontal conditions, the intima–media thickness of carotid arteries and circulating biomarkers were examined.
Results: Subjects with moderate to severe CP exhibited an increased risk of high EPC count, compared with those with no or mild CP: CD34⁺/KDR⁺ EPC [odds ratio (OR)=9.5, 95% confidence interval (95% CI) 1.5–61.0, p= 0.018; CD133⁺/KDR⁺ EPC, OR=4.6, 95% CI 1.1–19.5, p =0.039]. C-reactive protein was significantly associated with high CD34⁺/KDR⁺ EPC count and age was inversely related with high EPC count. Age, gender and CD34⁺/KDR⁺ EPC were independent variables of increased carotid intima–media thickness ( p <0.05).
Conclusion: This study shows for the first time that moderate to severe CP is associated with an increased level of circulating EPC.     

Significance of oral examination in chronic graft-versus-host disease

Fourteen patients who received allogeneic bone marrow transplantation (BMT) were examined 100 to 220 days after BMT. Ten out of 14 patients were diagnosed as having chronic graft-versus-host disease (cGVHD) in skin, liver, eyes and other organs. These cGVHD patients also had objective evidence of oral involvement. Subjective xerostomia was experienced by 7 cGVHD patients and decreased whole saliva flow was observed in 4 cGVHD patients. However, no patient had a history of parotid swelling or notable abnormality in parotid sialography. Labial salivary glands (LSG) of 9 cGVHD patients showed atrophy and/or destruction in association with diffusely infiltrating lymphocytes. The infiltrating lymphocytes were mainly CD3⁺ T cells with a predominance of CD8⁺ cells over CD4⁺ cells. Lichenoid lesions on the oral mucosa were also observed in 5 cGVHD patients. Thus, this study indicated that oral examination, including LSG biopsy, is useful in the diagnosis of cGVHD.     

口腔扁平苔藓患者外周血T-bet和GATA-3mRNA表达及意义

目的:探讨转录因子T-bet及GATA-3在口腔扁平苔藓(oral lichen planus,OLP)发病中的作用及意义。方法:采用RT-PCR技术测定30例OLP患者以及30例健康人外周血单个核细胞(PBMC)中T-bet和GATA-3 m RNA的表达水平。结果:OLP组及分型后各组T-bet mRNA的表达水平均高于对照组,差异有统计学意义(P<0.05);OLP组及糜烂型OLP组GATA-3 mRNA表达水平高于对照组,差异有统计学意义(P<0.05),非糜烂型OLP组与对照组差异无统计学意义(P>0.05);T-bet/GATA-3比值各组差异均无统计学意义(P>0.05)。结论:T-bet和GATA-3 mRNA的表达增高可能是OLP发病的重要原因,且GATA-3mRNA的表达变化与OLP临床类型有关。     

Immunocompetent cells in rat periodontal ligament and their recruitment incident to experimental orthodontic tooth movement

The aims of this study were to evaluate the number and distribution of immunocompetent cells in normal rat periodontal ligament (PDL) and to quantify their recruitment incident to experimental tooth movement. 27 young animals had the 1st right maxillary molar moved mesially by an orthodontic appliance for 1, 3, 7 and 14 days, respectively. 4 animals served as untreated controls. An immunohistochemical procedure was carried out on alternate serial cryostat sections, and monoclonal antibodies against CD1 II (macrophages, dendritic cells), CD43⁺ (lymphocytes, polymorphs), CD4 (helper T-lymphocytes), and class II MHC molecules were used. Mean counts of the immunolabeled cells in the control group showed the highest number of GDI lb⁺ and class II molecule expressing cells, while CD4⁺ and CD43⁺ cells were scarcely found. Significant increase in the number of CD1 lb⁺, CD43⁺ cells and class II molecules was found in the PDL of the experimentally moved 1st molars compared with the contralateral side and the control group, while CD4⁺ cells showed no significant increase. CD11b⁺ and cells expressing class II molecules were found around hyalinized tissue, between dentin and cellular cementum and close to Malassez'epithelial cells. In conclusion, normal rat PDL has high number of macrophage and dendritic-like cells, but few lymphocytes and granulocytes. Furthermore, experimental tooth movement leads to significant recruitment of cells belonging to the mononuclear phagocytic system, but has no significant effect on the number of lymphocytes and granulocytes in the rat PDL.     

Epithelial dendritic cells in pathological human oral tissues

Epithelial dendritic cells (EDC) were examined in human oral tissues with non-specific keratosis, lichen planus and squamous cell carcinoma. Acetone-fixed frozen sections were stained using an indirect immunoperoxidase technique and monoclonal antibodies to the human CD1 thymocyte (OKT6) and HLA-DR antigens. Significantly more T6⁺ and DR⁺ EDC were present in lichen planus tissues than normal controls, tissues with non–specific keratosis and the epithelia overlying/adjacent to squamous cell carcinomas, the latter tissues having comparable numbers of both T6⁺ and DR⁺ EDC. By contrast, significantly fewer T6⁺ EDC and significantly more DR⁺ cells were present in the invasive epithelium of squamous cell carcinomas than the overlying/adjacent epithelium of carcinomas, the non-specific keratosis group and the normal tissues. 23–60% of pathological tissues had either focal or general DR⁺ reactivity in keratinocytes, but there was no correlation between the density of T6⁺ or DR⁺ EDC and the keratinocyte DR status of the tissues. The results suggest that immunological enhancement occurs in lichen planus and possibly immunological impairment may characterize invasive squamous cell carcinoma.     

An immunocytochemical study of the inflammatory cell infiltrate and epithelial expression of HLA-DR in odontogenic cysts

The presence and distribution of lymphocytes, Langerhans cells, HLA-DR' infiltrating cells and the expression of HLA-DR by lining epithelium was investigated in the walls of odonlogenic cysts using an indirect immunoperoxidase method on acetone-fixed cryostat sections. The 23 cysts studied consisted of 14 dental (radicular) cysts, 5 keratocysts, 2 dentigerous cysts, 1 surgical ciliated cyst and 1 incisive canal cyst. The cell populations detected in the walls of all cysts were similar and consisted of HLA-DR+ macrophage-type cells and a mixture of T and B lymphocytes. Analysis of the T cell subsets revealed that in all cases the CD4⁺, T_h/i subset predominated over the CD8⁺, T_s/c subset. 18/22 cyst linings contained cells expressing a Langerhans cell phenotype (CD1⁺). Cytoplasmic epithelial expression of HLA-DR was detected in 7/22 specimens. Neither the presence of HLA-DR⁺ epithelial cells nor LC were restricted to a given type of cyst. These findings indicate the occurrence of similar cellular processes irrespective of the proposed developmental or inflammatory aetiology of these lesions.     

Role of distinct CD4+ T helper subset in pathogenesis of oral lichen planus

Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T‐cell‐mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4⁺ T helper (CD4⁺ Th) cells appeared as the major lymphocytes. These CD4⁺ T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4⁺ Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4⁺ Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment.