FAS和FASL基因在大鼠胸腺细胞凋亡时的表达及其意义

目的检测FAS和FASL基因在Wistar大鼠胸腺细胞凋亡的表达,探讨细胞凋亡调控基因在大鼠胸腺细胞凋亡时的作用。方法采用原位标记(TUNEL)法检测DNA单链或双链的裂解;应用免疫组织化学染色法,观察不同剂量糖皮质激素诱导的大鼠胸腺细胞凋亡时FAS和FASL基因的表达。结果镜观察地塞米松组TUNEL阳性细胞较多并且分散在皮质各处。免疫组织化学结果表明,正常对照组胸腺内FAS呈低表达,随着地塞米松剂量的增加FAS的表达成递增趋势,地塞米松各组与对照组比较差异有统计学意义(P0.05);正常对照组胸腺内FASL呈高表达,随着地塞米松剂量的增加FASL的表达成递减趋势,地塞米松各组与对照组比较差异有统计学意义(P0.05)。结论促凋亡蛋白FAS和抗凋亡蛋白FASL在糖皮质激素诱导引起的胸腺细胞凋亡调控中起重要作用。     

BALB/c小鼠胸腺巨噬细胞不同亚群特性研究

目的研究小鼠胸腺巨噬细胞组成、分布、形态、功能。方法糖皮质激素诱导小鼠胸腺细胞凋亡,采用免疫荧光染色法,免疫组织化学和酸性磷酸酶(ACP)双重染色方法,发现小鼠胸腺巨噬细胞的不同表型。结果发现小鼠胸腺巨噬细胞存在四种表型:树状突起型细胞:可被Mac-2,F4/80单克隆抗体标记,数量最多,分布于整个胸腺实质且有吞噬作用;扁平型细胞:可被F4/80单克隆抗体标记,分布于皮质被膜下方;小卵圆型细胞:可被Mac-2单克隆抗体标记,分布于胸腺髓质和皮髓交界(CMR),此类细胞未见吞噬现象。ED1~+细胞:细胞形态不规则,主要分布于皮髓质交界区。以上不同的巨噬细胞亚群均可显示酸性磷酸酶活性。结论小鼠胸腺巨噬细胞存在不同亚群,表现在其组成、形态、分布、特点及功能差异等方面。     

BAD和Bcl-X/L基因在小鼠胸腺细胞凋亡时的表达及其意义

目的检测BAD和Bcl-X/L基因在小鼠胸腺细胞凋亡的表达,探讨细胞凋亡调控基因在小鼠胸腺细胞凋亡时的作用。方法应用免疫组织化学染色法,观察不同剂量糖皮质激素诱导的小鼠胸腺细胞凋亡时BAD和Bcl-X/L基因的表达。结果免疫组织化学结果表明,正常对照组胸腺内BAD呈低表达,地塞米松组随剂量的增加BAD的表达成递增趋势,地塞米松各组与对照组比较差异有有统计学意义(P<0.05);正常对照组胸腺内Bcl-X/L呈高表达,地塞米松组随剂量的增加Bcl-X/L的表达成递减趋势,地塞米松各组与对照组比较差异有统计学意义(P<0.05)。结论促凋亡蛋白BAD和抗凋亡蛋白Bcl-X/L在糖皮质激素诱导引起的胸腺细胞凋亡调控中起重要作用。     

胸腺基质细胞对热应激小鼠胸腺细胞亚群变化及HSP70表达的影响

目的探讨胸腺基质细胞(TSC)对热应激小鼠胸腺细胞的调节作用。方法应用光镜、电镜、流式细胞术等观察初代培养的TSC对热应激胸腺细胞发育的调节作用。结果 TSC可大量粘附和吞噬胸腺细胞,使热应激胸腺细胞数量明显减少,但尚存的胸腺细胞中活细胞比例却明显增加,凋亡率明显减少。TSC可促进热应激胸腺细胞HSP70表达增加,使热应激胸腺细胞的DP及SP细胞,尤其是DP细胞数量明显减少。结论 TSC可清除大量的热应激胸腺细胞,TSC促进热应激胸腺细胞HSP表达增高可能具有双重意义:既可保护胸腺细胞,又可促进TSC识别和吞噬已受损的或凋亡的胸腺细胞。     

Protection of growth hormone on apoptosis of murine thymocytes induced by dexamethasone

目的:研究生长激素(GH)对地塞米松(Dex)诱导小鼠胸腺细胞凋亡的作用及机制.方法:建立地塞米松诱导小鼠胸腺细胞凋亡模型,通过观察小鼠胸腺指数的变化、形态学改变,TdT缺口末端标记(TUNEL)及流式细胞仪检测,研究生长激素影响胸腺细胞凋亡情况,并运用免疫组织化学观察生长激素对小鼠胸腺凋亡蛋白Bax和Bcl-2表达的调节.结果:经生长激素处理后,电镜下观察小鼠胸腺细胞凋亡现象明显改善;TUNEL检测和流式细胞仪检测结果显示,胸腺细胞凋亡数量减少;图像分析系统测定光密度值显示,生长激素处理组小鼠胸腺细胞中Bax表达较模型组降低,Bcl-2表达增加.结论:生长激素对地塞米松诱导的小鼠胸腺细胞凋亡具有一定的抑制作用,这种作用可以通过调节凋亡蛋白Bax、Bcl-2的表达等途径实现.     

胸腺因子对小鼠腹腔巨噬细胞的作用

据报道胸腺因子能诱导前T淋巴细胞分化、发育、成熟变为有免疫功能的T细胞,对机体超免疫促进作用。我们用胸腺因子作用小鼠,观察其对小鼠腹腔巨噬细胞吞噬活力的影响和代表巨噬细胞活性的酸性磷酸酶(ACP)和酸性非特异性酯酶(ANAE)的变化,以探讨胸腺因子对有免疫功能的巨     

胸腺细胞分化发育的凋亡调控

胸腺细胞在胸腺内的发育过程经历了TCR基因重排与表达、阳性选择和阴性选择三个主要过程。凋亡,又称程序性细胞死亡,在胸腺细胞发育过程贯穿始终,因此研究胸腺内T细胞发育过程中的凋亡对揭示胸腺选择作用和中枢耐受形成机制有重要意义。本文就胸腺细胞在胸腺内发育过程中凋亡的发生及其调控作一综述。     

细胞凋亡与肺癌

<正>凋亡（apoptosis）,也即程序性细胞死亡,是由基因控制的细胞的自我消亡。细胞凋亡的基本过程是细胞表面分子接到诱导因子刺激并将信号传入细胞内部,触发细胞内部的死亡程序,导致细胞死亡。此过程发生紊乱将导致发育异常和肿瘤发生。同样,在肿瘤中也存在凋亡,癌细胞中仍然保持着这种自杀程序。不过是存活细胞的数量和存活时间超过了死亡细胞。本文将就近年来有关肺癌与细胞凋亡的关系予以综述。1 细胞凋亡的特征 凋亡的概念由Wyllie在1972年首先提出,apoptosis的本意为秋天的树叶从树上凋落,在此形容凋亡细胞形成凋亡小体从细胞上脱落,继而被吞噬细胞吞噬。细胞凋亡的一个最直观的指标就是DNA的片断化,DNA在核小体之间被切断,成为180bp及其倍数大小的一系列DNA,经核酸电泳后就能得到一个DNA阶梯。目前了解较多的可介导DNA片段化的酶有三种:NUC-18、DNase Ⅰ和DNase Ⅱ。而内切酶活性依赖于钙和镁离子,并受到锌离子的抑制。 Darzynkiewicz等用流式细胞仪观察到细胞凋亡具有以下特征:1.由于细胞核酸内切酶激活,使得DNA特异性荧光染色减少;2.细胞浆膜完整;3.线粒体仍有跨膜电位;4.保留了ATP依赖的溶酶体质子泵;5.蛋白含量明显减少,原因是内源性内切酶被激活;6.凋亡发生于G_0期胸腺细胞;7.前向散射减少     

固相PF18-3单抗促进亚适量ConA诱导的胸腺细胞活化后凋亡

目的　研究PF18 3单抗识别分子和胸腺细胞活化及凋亡的关系。方法　应用3H TdR掺入实验及流式细胞术 (FACS)技术 ,分析了胸腺细胞与固相单抗PF18 3共育后细胞活化过程中3H TdR掺入、细胞周期及DNA亚二倍体变化、早期活化及凋亡分子的表达。结果　固相单抗PF18 3有弱的促胸腺细胞3H TdR掺入和促进CD2 5的表达 ,当有亚适量ConA存在时作用更明显。与对照组相比 ,PF18 3及亚适量ConA共育后 ,2 4、48h时活细胞数量减少。细胞周期分析 ,G0 /G1期细胞相对减少 ,S期相对增多 ,但G2 /M期无明显变化。凋亡相关分析 ,共育后 2 4、48h时DNA亚二倍体阳性细胞及 12h时AnnexinV结合阳性细胞增多。结论　PF18 3单抗识别分子能协同亚适量ConA对胸腺细胞的活化 ,并诱导胸腺细胞活化后凋亡     

小鼠胚胎肾程序性细胞死亡行为的超微结构变化

目的:观察小鼠胚胎肾发育过程中程序性细胞死亡行为的超微结构变化.方法:应用透射电子显微镜技术对不同胚龄(E12、14、16、18 d)胎鼠的肾程序性细胞死亡进行系统观察.结果:在小鼠胚胎肾中,细胞凋亡多见,出现在肾发育的各个时期和各个结构中,程序性坏死和副凋亡少见,只出现在发育中的肾单位内.程序性细胞死亡的结局包括被吞噬、被血流带走和经尿液排出.结论:细胞凋亡、程序性坏死和副凋亡构成了小鼠胚胎肾发育过程中的程序性细胞死亡,以细胞凋亡为主,程序性坏死和副凋亡为辅.肾发育过程中程序性死亡的细胞尸骸经尿液排出是一个与肾结构特征有关的处理方式.     

DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo

Thymocyte death has been recognized as one of the best models for studying apoptosis. Our recent study, however, indicated that most thymocytes die without DNA fragmentation and become terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling-positive (TUNEL⁺) only after being phagocytosed by macrophages. In this study, we used histological techniques using the TUNEL method, histochemistry, immunohistochemistry, and transmission electron microscopy as well as flow cytometry to examine in vivo the effect of glucocorticoid (GC), a well-known agent for inducing thymocyte apoptosis in vitro, on thymocyte death to determine whether or not DNA fragmentation was the first event of GC-induced thymocyte death. At 2 h and 4 h after GC injection, a large number of cortical thymocytes were TUNEL⁺. Most TUNEL⁺ cells were aggregated to form clusters. Double staining of the section showed that the TUNEL⁺ thymocytes were phagocytosed by acid phosphatase⁺ and Mac-2⁺ macrophages. An ultrastructural study indicated that a far greater number of small pyknotic thymocytes were present in the cortex of the GC-treated thymus than were observed in the control thymus, that all those pyknotic thymocytes were TUNEL^?, and moreover, that at the electron microscopic level, TUNEL⁺ cells were all phagocytosed by macrophages. Flow cytometric analysis did not detect a single TUNEL⁺ thymocyte even 4 h after the GC treatment, suggesting that virtually no free dead thymocytes were present after DNA fragmentation. These results indicate that, consistent with our previous findings with normal thymocyte death and B cell death in the germinal centers, DNA fragmentation is not involved in the cell death process of the GC-induced rapid thymocyte death in vivo.     

Death of germinal center B cells without DNA fragmentation

During the selection of B cells within germinal centers (GC) on the basis of their affinity for T-dependent antigen, B cells not positively selected are eliminated within GC. This process of B cell death has been considered to be apoptosis. In a recent study, we have reported that, although a substantial number of thymocytes were considered to be dead because of their extremely small cell size and heavy chromatin condensation even though they were not yet phagocytosed (pyknosis), they were devoid of DNA fragmentation, the most characteristic feature for apoptosis. In this study, we examined in vivo the mechanism of B cell death within GC by using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method to detect DNA double-strand breaks. TUNEL⁺ B cells were scattered throughout the upper dark and the light zones of GC. Double staining of the sections by the TUNEL method and acid phosphatase (AcP) activities showed that all the TUNEL⁺ B cells were phagocytosed by macrophages. Light microscopic and ultrastructural studies revealed the presence of small unphagocytosed B cells within the light zone. These cells are undoubtedly dead because they were much smaller than surrounding lymphoid cells and have a heavy chromatin condensation. Furthermore, ultrastructural detection of DNA fragmentation confirmed that these small unphagocytosed B cells were TUNEL^?, implying that DNA fragmentation is not primarily involved in the cell death process of these small dead B cells. These results indicate that most B cells, not positively selected and thus destined to be eliminated, die within GC without DNA fragmentation, and are subsequently phagocytosed by macrophages and become TUNEL⁺. Typical apoptosis, characterized by DNA fragmentation in situ, is not the predominant type of cell death that occurs during the selection of B cells in GC.     

Nonylphenol-induced thymocyte apoptosis involved caspase-3 activation and mitochondrial depolarization

Although the effect of 4-nonylphenol on cells of immune system have long been recognized, little is known about the effect of 4-nonylphenol on the induction of apoptosis and related signaling events in the lymphoid cells. In the present study, we used cultured thymocytes of mice to investigate the ability of 4-nonylphenol to induce the apoptosis of thymocytes and to explore the role of signal transduction pathway leading to apoptosis. The results showed that the cytotoxic effects of 4-nonyphenol involved DNA fragmentation (DNA ladder), characteristic of apoptosis. Staining of 4-nonyphenol-treated thymocytes with DNA-binding fluorochrome Hoechst 33258 showed the typical apoptotic nuclei condensation and fragmentation of chromatin. The rates of apoptosis of the 4-nonylphenol-treated thymocytes increased significantly at 4 and 6 h, which were determined by analysis of hypodiploid cells and FITC-Annexin V and PI double staining. Flow cytometer analysis also revealed that the loss of mitochondrial membrane potential and increased activity of caspase-3 occurred concomitantly with the onset of 4-nonyphenol-induced apoptosis. Furthermore, a caspase-3 inhibitor, z-DEVD-fmk protected thymocytes from apoptosis induced by 4-nonyphenol. These results suggest that 4-nonylphenol induces thymocyte apoptosis via caspase-3 activation and mitochondrial depolarization.     

胸腺细胞凋亡的电镜观察和DNA裂解原位标记

目的：观察胸腺细胞凋亡的超微结构及其与ＤＮＡ裂解的相互关系。方法：对大鼠进行腹腔内糖皮质激素注射，对胸腺进行光、电镜观察，并作ＴｄＴ介导的ｄＵＴＰ缺口末端标记（ＴｄＴ－ｍｅｄｉａｔｅｄ－ｄＵＴＰｎｉｃｋｅｎｄｌａｂｅｌｉｎｇ，ＴＵＮＥＬ）。结果：皮质胸腺细胞出现凋亡的超微结构改变，少数细胞出现管网状结构。ＴＵＮＥＬ可标记不同阶段的凋亡细胞。结论：糖皮质激素可引起胸腺皮质细胞凋亡，上皮性网状细胞对凋亡细胞具有活跃的吞噬和降解作用。ＴＵＮＥＬ可选择性标记石蜡切片中的凋亡细胞，但对凋亡的判定需结合形态特点并与坏死鉴别     

Cell death in denervated skeletal muscle is distinct from classical apoptosis

Denervation of skeletal muscle is followed by the progressive loss of tissue mass and impairment of its functional properties. The purpose of the present study was to investigate the occurrence of cell death and its mechanism in rat skeletal muscle undergoing post-denervation atrophy. We studied the expression of specific markers of apoptosis and necrosis in experimentally denervated tibialis anterior, extensor digitorum longus and soleus muscles of adult rats. Fluorescent staining of nuclear DNA with propidium iodide revealed the presence of nuclei with hypercondensed chromatin and fragmented nuclei typical of apoptotic cells in the muscle tissue 2, 4 and to a lesser extent 7 months after denervation. This finding was supported by electron microscopy of the denervated muscle. We found clear morphological manifestations of muscle cell death, with ultrastructural characteristics very similar if not identical to those considered as nuclear and cytoplasmic markers of apoptosis. With increasing time of denervation, progressive destabilization of the differentiated phenotype of muscle cells was observed. It included disalignment and spatial disorganization of myofibrils as well as their resorption and formation of myofibril-free zones. These changes initially appeared in subsarcolemmal areas around myonuclei, and by 4 months following nerve transection they were spread throughout the sarcoplasm. Despite an increased number of residual bodies and secondary lysosomes in denervated muscle, we did not find any evidence of involvement of autophagocytosis in the resorption of the contractile system. Dead muscle fibers were usually surrounded by a folded intact basal lamina; they had an intact sarcolemma and highly condensed chromatin and sarcoplasm. Folds of the basal lamina around the dead cells resulted from significant shrinkage of cell volume. Macrophages were occasionally found in close proximity to dead myocytes. We detected no manifestations of inflammation in the denervated tissue. Single myocytes expressing traits of the necrotic phenotype were very rare. A search for another marker of apoptosis, nuclear DNA fragmentation, using terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling (the TUNEL method) in situ, revealed the presence of multiple DNA fragments in cell nuclei in only a very small number of cell nuclei in 2 and 4 month denervated muscle and to less extent in 7 month denervated muscle. Virtually no TUNEL reactivity was found in normal muscle. Double labeling of tissue denervated for 2 and 4 months for genome fragmentation with the TUNEL method and for total nuclear DNA with propidium iodide demonstrated co-localization of the TUNEL-positive fragmented DNA in some of the nuclei containing condensed chromatin and in fragmented nuclei. However, the numbers of nuclei of abnormal morphology containing condensed and/or irregular patterns of chromatin distribution, as revealed by DNA staining and electron microscopy, exceeded by 33-38 times the numbers of nuclei positive for the TUNEL reaction. Thus, we found a discrepancy between the frequences of expression of morphological markers of apoptosis and DNA fragmentation in denervated muscle. This provides evidence that fragmentation of the genomic DNA is not an obligatory event during atrophy and death of muscle cells, or, alternatively, it may occur only for a short period of time during this process. Unlike classical apoptosis described in mammalian thymocytes and lymphoid cells, non-inflammatory death of muscle fibers in denervated muscle occurs a long time after the removal of myotrophic influence of the nerve and is preceded by the progressive imbalance of the state of terminal differentiation. Our results indicate that apoptosis appears to be represented by a number of distinct isotypes in animals belonging to different taxonomic groups and in different cell lineages of the same organism.     

Developmental shift in TcR-mediated rescue of thymocytes from glucocorticoid-induced apoptosis

Glucocorticoid hormone (GC) production by thymic epithelial cells influences TcR signalling in DP thymocytes and modifies their survival. In the present work, we focused on exploring details of GC effects on DP thymocyte apoptosis with or without parallel TcR activation in AND transgenic mice, carrying TcR specific for pigeon cytochrome C, in vivo. Here we show that the glucocorticoid receptor (GR) protein level was the lowest in DP thymocytes, and it was slightly down-regulated by GC analogue, anti-CD3, PCC and combined treatments as well. Exogenous GC analogue treatment or TcR stimulation alone lead to marked DP cell depletion, coupled with a significant increase of early apoptotic cell ratio (AnnexinV staining), marked abrogation of the mitochondrial function in DP cells (CMXRos staining), and significant decrease in the Bcl-2(high) DP thymocyte numbers, respectively. On the other hand, the simultaneous exposure to these two proapototic signals effectively reversed all the above-described changes. The parallel analysis of CD4 SP cell numbers, AnnexinV, CMXRos, Bcl-2 and GR stainings revealed, that the GR and TcR signals were not antagonistic on the mature thymocytes. These data provide experimental evidence in TcR transgenic mice, in vivo, that when TcR activation and GR signals are present simultaneously, they rescue double positive thymocytes from programmed cell death. The two separate signalling pathways merge in DP thymocytes at such important apoptosis regulating points as the Bcl-2 and GR, showing that their balanced interplay is essential in DP cell survival.     

Galactoside-specific plant lectin,Viscum album agglutinin-I induces enhanced proliferation and apoptosis of murine thymocytes in vivo

Galactoside-specific plant lectin, Viscum album agglutinin-I (VAA-I) has been shown to act as a biomodulator with proinflammatory and apoptosis-inducing effects, however its cellular targets and mechanism of immunobiological action in vivo are less well understood. Therefore, in the present work the short- and long-term in vivo effects of VAA-I on thymocyte subpopulations and peripheral T cells were tested using a murine (Balb/c) model. Cell surface CD4/CD8 staining and flow cytometry allowed us to follow the changes of thymocyte subpopulations: CD4-CD8- double negative (DN), CD4+CD8+ double positive (DP), CD4+ or CD8+ single positive (SP) and mature peripheral T cells after single or repeated injections with low doses of VAA-I. The apoptosis of the cells was detected by flow cytometry using propidium iodide (PI) and Annexin V staining. To detect the short-term effects of the lectin, the animals were investigated 24 h after a single injection of 1 or 30 ng/kg body weight (BW) VAA-I+/-1 mg/kg Dexamethasone (DX). The total number of mature CD8+ SP thymocytes increased significantly with an enhancement of the ratio of apoptotic cells. In contrast, in the blood samples an elevated CD4/CD8 ratio was found. In the next trial, Balb/c mice were treated twice weekly with 1 or 30 ng/kg VAA-I+/-1 mg/kg DX for 3 weeks. The total cell count of thymocytes showed significant increases after both doses of VAA-I, but an elevated percentage of apoptotic cells was found only after treatment with 30 ng/kg VAA-I. SP thymocytes revealed higher increases in lectin-induced apoptosis than DN or DP cells. In addition, both lectin doses significantly inhibited the DX-induced reduction of all thymocyte subpopulations investigated. In conclusion, our data suggest that VAA-I is able to modulate the maturation of thymocytes in vivo.     

Haematopoietic antigen-presenting cells in the human thymic cortex: evidence for a role in selection and removal of apoptotic thymocytes

Only a small proportion of thymocytes survive T cell selection in the thymus and leave the thymus as mature T cells. The vast majority of thymocytes undergo cell death during selection, either due to failure to undergo positive selection on self peptide-MHC presented by thymic antigen presenting cells (APC) or due to negative selection. In the murine thymus it has been shown that most thymocytes that fail selection undergo apoptosis in the thymic cortex and are removed by cortical macrophages. However, it is unknown how apoptotic thymocytes are cleared from the cortex of the human thymus. Here we report the identification of antigen-presenting cells of haematopoietic origin (hAPCs) by expression of dendritic cell (DC) specific C-type lectin DC-SIGN (CD209) in the cortex of the human thymus, and show that these cells exhibit features of both immature DCs and macrophages. The analysis of cellular markers, in particular the expression of the molecular chaperone HLA-DM, on cortical hAPCs further suggests that these hAPCs may participate in selection of thymocytes in the cortex. Using in situ terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), we demonstrated that these cortical hAPCs are surrounded by apoptotic, TUNEL(+) thymocytes in situ. Futhermore, in situ immuno-cryo-electron microscopy suggests that cortical hAPCs take up and remove apoptotic thymocytes. Thus, DC-SIGN(+) hAPCs in the human thymic cortex appear to function in thymocyte selection and removal of apoptotic thymocytes from the thymic cortex.     

Butyric acid-induced apoptosis of murine thymocytes, splenic T cells, and human Jurkat T cells.

The purpose of this study was to examine the effect of butyric acid, an extracellular metabolite from periodontopathic bacteria, on apoptosis induction in murine thymocytes, splenic T cells, and human Jurkat T cells. Butyric acid significantly suppressed T-cell viability in both a concentration- and time-dependent fashion. The results of DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in thymocytes (with 1.25 mM butyric acid and 6 h after treatment) and in splenic T cells and Jurkat cells (with 2.5 mM butyric acid and 16 h after treatment). Incubation of thymocytes or Jurkat cells with 5 mM butyric acid for 21 h resulted in the typical ladder pattern of DNA fragmentation. Furthermore, Jurkat cells treated with 5 mM butyric acid showed the characteristic pattern of apoptotic cells such as chromatin condensation and hypodiploid nuclei. Experiments with fractionated subpopulations of splenic T cells revealed that DNA fragmentation was predominantly observed in CD4+ T cells. Butyric acid-induced apoptosis of thymocytes was decreased by the protein kinase inhibitors H7 and staurosporine. These inhibitors were less effective with similarly treated splenic T cells and Jurkat cells. These data suggest that butyric acid, one of the volatile fatty acids produced by periodontopathic bacteria and one that easily penetrates the oral mucosa, can modulate the immunoregulatory cell population in periodontal tissue by inducing T-cell death through apoptosis.