Th1细胞/Th2细胞在口腔扁平苔藓发病机制中的作用

口腔扁平苔藓是最常见口腔黏膜疾病之一,发病机制尚不明确,因其具有癌变潜能,WHO将其列为癌前状态。研究发现,Th1细胞/Th2细胞亚群与口腔扁平苔藓的发病密切相关,尤其是Th1/Th2漂移学说与OLP的关系成为近年研究热点。下文针对Th1细胞/Th2细胞在口腔扁平苔藓中的最新研究成果做一综述和展望。     

乳腺癌中OPN、CD44v6及CD10的表达及其临床意义

目的探讨骨桥蛋白(osteopontin,OPN)、CD44v6、CD10在乳腺癌及腺病中的表达,分析三者与乳腺癌临床病理特征及预后的相关性。方法采用免疫组化En Vision两步法检测OPN、CD44v6、CD10在浸润性癌非特指型(153例)、导管原位癌(40例)、腺病(28例)中的表达;采用χ2检验分析三者与乳腺癌临床病理特征的关系,多因素分析采用Cox回归模型,预后分析采用Kaplan-Meier法,组间差异比较采用Log-rank检验。结果在腺病、导管原位癌、浸润性癌非特指型中,OPN阳性率分别为7.1%、27.5%、56.2%,CD44v6阳性率分别为10.7%、40.0%、57.5%,CD10阳性率分别为3.5%、37.5%、55.6%。三者在腺病中的阳性率均低于乳腺癌,差异具有统计学意义(P=0.020、0.042、0.003)。浸润性癌非特指型组织中OPN、CD44v6和CD10的表达均与组织学分级、淋巴结转移相关,且OPN、CD44v6表达均与p TNM分期相关,CD44v6表达与PR状态相关(P均0.05);在导管原位癌中三者的表达与核分级相关,差异均有统计学意义(P均0.05);三者的表达与患者年龄、绝经状态、脉管浸润、Ki-67增殖指数、ER状态、HER-2状态均无关(P均0.05)。OPN、CD44v6和CD10在乳腺癌中的表达两两间均呈正相关(P均0.001)。多因素分析提示淋巴结转移、CD10阳性是浸润性癌非特指型患者的预后影响因素。生存分析显示在浸润性癌非特指型中,三者均阴性组患者的无病生存率(disease-free survival,DFS)、总生存率(overall survival,OS)均优于三者均阳性组,差异有统计学意义(P=0.010、0.007)。结论 OPN、CD44v6、CD10在乳腺癌中高表达,均与乳腺癌进展相关。联合检测OPN、CD44v6、CD10在乳腺癌中的表达,对于判断患者预后具有重要价值。     

Recruitment of dendritic cells in oral lichen planus

Using immunohistochemistry the presence of different dendritic cell (DC) subsets was analysed in 16 biopsies from patients with oral lichen planus (OLP). A significant increase of CD1a+/Langerin+ Langerhans cells, DC-SIGN+ DC and CD123+/BDCA2+ plasmacytoid DCs (PDCs) was found in the epithelium and in the stroma of OLP biopsies compared to normal oral mucosa. A proportion of DCs were mature DC-LAMP+ and expressed S100 or CD11c, typically found in the interdigitating DCs of nodal T-cell areas. Double staining revealed that mature DCs co-expressed CCR7, thus indicating the development of a nodal migratory phenotype upon maturation. Significant recruitment of PDCs producing IFN-alpha was demonstrated by the expression of MxA within the lichenoid inflammatory infiltrate and close cell-to-cell contacts between PDCs and mature DCs were observed, with a significant correlation between the numbers of these two populations. Moreover, PDCs were also found to contain Granzyme-B, an associated-cytotoxic granule protein, inducing target cell apoptosis. Taken together, these results suggest that PDCs may promote maturation of DCs and amplify the cytotoxicity of lymphoid cells. Finally, the recruitment of different subtypes of DC, such as Langerhans cells, stromal DC-SIGN+ DCs and PDCs, associated with a significant proportion of mature DCs, acquiring a CCR7+ 'migratory' phenotype, indicate that they may play a pivotal role in the development of the lichenoid inflammatory infiltrate that occurs typically in OLP.     

Alteration of the Expression of CD4 Isoforms in Oral Epithelia and Saliva from Patients with Oral Lichen Planus

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that cell-mediated immunological mechanisms are involved in pathogenesis. The objective of this study was to investigate the expression of CD44 isoforms including CD44s, CD44v5, and CD44v6 in biopsy specimens and saliva from OLP patients. Thirty-one OLP patients and 30 healthy subjects were enrolled in this study. Immunohistochemical methods were used to detect the expression of CD44 isoforms in oral epithelia, and enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of salivary CD44 isoforms. Our results demonstrated that expression of CD44v6 in oral epithelia from OLP patients was significantly decreased in comparison to controls (p = 0.021). Levels of salivary CD44s and CD44v5 from OLP patients were significantly higher than those from controls (p = 0.007 and p = 0.002, respectively). In summary, our findings provided additional evidence that the pathological stress, such as chronic inflammation, altered the expression of CD44 isoforms in oral epithelia and saliva of OLP patients.     

Alteration of the Expression of CD4 Isoforms in Oral Epithelia and Saliva from Patients with Oral Lichen Planus

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that cell-mediated immunological mechanisms are involved in pathogenesis. The objective of this study was to investigate the expression of CD44 isoforms including CD44s, CD44v5, and CD44v6 in biopsy specimens and saliva from OLP patients. Thirty-one OLP patients and 30 healthy subjects were enrolled in this study. Immunohistochemical methods were used to detect the expression of CD44 isoforms in oral epithelia, and enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of salivary CD44 isoforms. Our results demonstrated that expression of CD44v6 in oral epithelia from OLP patients was significantly decreased in comparison to controls (p = 0.021). Levels of salivary CD44s and CD44v5 from OLP patients were significantly higher than those from controls (p = 0.007 and p = 0.002, respectively). In summary, our findings provided additional evidence that the pathological stress, such as chronic inflammation, altered the expression of CD44 isoforms in oral epithelia and saliva of OLP patients. An erratum to this article can be found at     

Soluble Fas antigen in the serum of women with oral lichen planus

Enzyme immunoassay showed that soluble Fas antigen is significantly more often detected in the serum of patients with oral lichen planus (72.5%) and oral squamous-cell cancer (75%) than in healthy postmenopausal women (36%). The level of soluble Fas antigen was significantly higher in patients with squamous-cell cancer and erosive ulcerative and exudative hyperemic lichen planus than in healthy women. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 672–674, June, 2007     

Serologic and molecular analysis of the HLA system in Israeli Jewish patients with oral erosive lichen planus

Abstract: Oral erosive lichen planus is a distinct subtype of the common dermatosis lichen planus. Although the etiology of lichen planus is still obscure, it is known that cell-mediated immune mechanisms and genetic factors underlie its pathogenesis. Previous studies have found an association between lichen planus and HLA-DR3 or DR9 in different population groups. The present work was designed to elucidate, at the serologic and molecular levels, whether and which HLA genes are associated with oral erosive lichen planus in Israeli Jewish patients. A significant association with HLA-DR2 (RR = 4.7; p_c < 0.0013) and a decrease in DR4 (RR = 0.3; p < 0.03) among the patients were noted. Oligotyping of DR2 alleles showed the presence of all three common variants (DRB1*1501, DRB1*1502 and DRB1*1601) in the patients, although none of the variants was overrepresented significantly. Three possible explanations for the role of HLA genes in the predisposition to oral erosive lichen planus are discussed. The most attractive theory for the pathogenesis of the disease seems to include the involvement of non-classical HLA genes.     

Involvement of CD44 variant isoforms in hyaluronate adhesion by human activated T cells

The standard, 85–95-kDa form of the hyaluronic acid (HA) receptor CD44 and a number of CD44 mRNA splice variants play important roles in immune responses and tumor metastasis. Variants carrying exon 6 (v6), or 9 (v9) products are transiently expressed on activated human T cells. Here, modulation experiments with specific monoclonal antibodies (mAb) indicate that v6 and v9 are expressed independently on distinct sets of CD44 molecules, and that their combined expression is necessary for HA adhesion. Moreover, the finding that mAb-mediated cross-linking of v6 and v9 promoted cytosolic free Ca²⁺ mobilization and co-stimulated CD3-triggered T cell proliferation indicates that v6 and v9 possess signaling and effector function activation ability. Finally, HA-mediated signaling appears to be required for variant-dependent adhesion to HA. The observation that soluble HA promoted cytosolic free Ca²⁺ mobilization indicates that HA-induced Ca²⁺ mobilization can occur during T cell-HA interaction. Since Ca²⁺ mobilization was inhibited by pretreatment of cells with an anti-CD44 mAb directed against the HA-binding domain of CD44, CD44 receptors appear to be involved in HA-mediated signal transduction. The requirement of cytosolic free Ca²⁺ for adhesion is shown by the fact that ionomycin (a Ca²⁺ ionophore) stimulated, and EGTA (a Ca²⁺ chelator), inhibited HA adhesion. In addition, cytoskeletal functional activation is required for cell adhesion to HA, since drugs that block actin polymerization, such as cytochalasin B, or actomyosin contraction, such as the calmodulin antagonist W-7, inhibited cell adhesion to HA. As this adhesion is also ADP ribosylation-sensitive, it may involve a GTP-dependent function of CD44v, i.e. ankyrin binding. Our data indicate that there is a functional hierarchy among the CD44 molecules expressed on human peripheral blood T cells and that the splice variants, as compared to the standard form, exhibit a greater HA binding ability which involves CD44-mediated signaling and effector function activation.     

FoxP3(+) T regulatory cells in oral lichen planus and its correlation with the distinct clinical appearance of the lesions

The aim of this study was to evaluate the presence of FoxP3⁺ cells in oral lichen planus (OLP) and to correlate the findings with clinical and histopathological features of these lesions. The sample consisted of 32 cases of OLP (17 reticular and 15 erosive cases) and 10 cases of inflammatory fibrous hyperplasia (IFH). Clinical examination, histopathological and histomorphometric analysis, and immunohistochemistry (anti‐FoxP3 antibody) were performed. Cells were counted in juxtaepithelial and intraepithelial regions of the lesions, and the results are expressed as the mean and range. Most erosive lesions were keratinized and exhibited epithelial atrophy, whereas most reticular lesions were hyperkeratinized. Mean epithelial thickness and mean density of the inflammatory infiltrate were higher in reticular lesions than in erosive OLP. Juxtaepithelial FoxP3⁺ cells were slightly more frequent in erosive lesions (mean: 1.7 and range: 0–9.4) than in reticular lesions (mean: 1.5 and range: 0–8.3). There was a significant difference in the frequency of these cells between OLP (mean: 1.6 and range: 0–9.4) and IFH (mean: 0.5 and range: 0–1.4) (P < 0.05). The number of intraepithelial FoxP3⁺ cells was higher in reticular OLP and IFH when compared with erosive lesions. The larger number of juxtaepithelial FoxP3⁺ cells in OLP compared to IFH might be related to the distinct etiopathogenesis of these lesions. High disease activity or action of the oral microbiota may explain the slightly higher frequency of FoxP3⁺ cells in erosive lesions.     

Interleukin-18 gene polymorphisms and haplotypes in patients with oral lichen planus: a study in an ethnic Chinese cohort

Interleukin (IL)-18, a proinflammatory cytokine, induces T-helper 1 differentiation and cytotoxic T-lymphocyte functions, both of which have been proposed in the pathogenesis of oral lichen planus (OLP) - an oral disease resembles oral mucosal graft-versus-host disease (GVHD) both clinically and histologically. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in the IL18 gene on the chromosome 11q22 in patients with OLP. Four SNPs of the IL18 gene at positions -137G/C (rs187238), -607C/A (rs1946518), -656G/T (rs1946519), and 1248A/G (rs189667) were analyzed in 151 patients with OLP and 143 normal controls using polymerase chain reaction-sequence-specific primers method, and the serum level of IL-18 protein was determined by enzyme-linked immunosorbent assay (ELISA). The data revealed that there is a significant difference in IL18-607 genotype distributions between the patient group and the control group (P < 0.001), and the polymorphism -137G/C also appears to be statistically associated with the more severe erosive subtype (eOLP) (P = 0.023). The identified polymorphisms at the IL-18 promoter region (i.e. -137GG) are likely to exert positive effect on the production of IL-18 protein in OLP, as detected by ELISA. Using phase software, four haplotypes were deduced from the two polymorphisms -607C/A and -137G/C, named haplotypes I to IV, and the haplotypes I, II, and IV are significantly associated with OLP (P < 0.001). Our data suggest that the identified IL18 polymorphisms may be associated with the pathogenesis of OLP in this Chinese cohort by upregulation of IL-18 production in vivo.     

Skew in T cell receptor usage with polyclonal expansion in lesions of oral lichen planus without hepatitis C virus infection

Oral lichen planus (OLP) is a refractory disorder of the oral mucosa. Its predominant symptoms are pain and haphalgesia that impair the quality of life of patients. OLP develops via a T cell-mediated immune process. Here, we examined the characteristics of the infiltrating T cells in terms of the T cell receptor (TCR) repertoires, T cell clonality, T cell phenotypes and cytokine production profiles. TCR repertoire analyses and CDR3 size spectratyping were performed using peripheral blood mononuclear cells (PBMCs) and tissue specimens of OLP biopsies from 12 patients. The cytokine expression profiles and T cell phenotypes were measured by real-time quantitative polymerase chain reaction. We observed that there were skewed TCR repertoires in the tissue samples (TCRVA8-1, VA22-1, VB2-1, VB3-1 and VB5-1) and PBMCs (TCRVA8-1, VB2-1, VB3-1 and VB5-1) from OLP patients. Furthermore, the CDR3 distributions in the skewed TCR subfamilies exhibited polyclonal patterns. We observed increases in CD4(+) T lymphocytes, interleukin (IL)-5, tumour necrosis factor (TNF)-alpha and human leucocyte antigen D-related in the OLP tissue specimens. Taken together, the present results suggest that T cells bearing these TCRs are involved in the pathogenesis of OLP, and that IL-5 and TNF-alpha may participate in its inflammatory process.     

A comparison of the pro-inflammatory, NF-κB-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients

To explore the feasibility of detection of the level of NF-κB-dependent cytokines in oral fluids from patient with oral lichen planus (OLP) for clinical application, 13 OLP subjects were enrolled in the study as were 13 age–sex-matched controls. In each subject, the whole unstimulated saliva (WUS), mixture of saliva and isotonic saline oral rinse (Saliva-NaCl), and lesion tissue transudates (TT) were collected by standard techniques. The level of cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids was determined by ELISA. In the three types of oral fluids, a significantly higher level of these cytokines was detected in OLP patients than in normal controls. These results indicate that NF-κB-dependent inflammatory cytokines may be detected at increased levels in certain oral fluids which may have diagnostic and prognostic potential for monitoring disease activity and making therapeutic decisions in patients with OLP.     

CD44 promotes resistance to apoptosis in human colon cancer cells

Overexpression of CD44, especially its variant isoforms, occurs consistently in colon cancer, as compared to autologous normal colon, and this change occurs also in most other types of cancer. One of the basic features of malignant transformation is the acquisition of resistance to apoptosis. In this study, we asked whether the expression of CD44 and some of its variant isoforms commonly found in colon cancer participate in resistance to apoptosis and what are the mechanisms involved. A human colon cancer cell line, SW620, which does not express CD44 was stably transfected with standard, v3-10, and v8-10 containing isoforms of CD44. Mock-transfected and CD44-transfected cells were exposed to etoposide to induce apoptosis. Apoptotic and concomitant changes relevant to the mechanisms of apoptosis were monitored by flow cytometry, DNA fragmentation, and immunoblot analyses. It was observed that resistance to apoptosis induced by etoposide is promoted by CD44 expression in SW620, and this resistance is better sustained by the full variant isoform, v3-10. Concomitant alterations in caspase 9, caspase 3, Bcl-xl, and Bak indicated that the resistance to apoptosis in this model involved the mitochondrial pathway. The differential response of CD44 transfectants was associated with a downregulation of pRb and phosphorylated AKT. The results of this study are consistent with the conclusion that expression of variant CD44 isoforms which is characteristic of colon cancer, and most other types of cancer, confers a selective advantage to resist apoptosis, thereby promoting cell transformation into a malignant phenotype, in conjunction with other anti-apoptotic factors.     

Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry

Odontogenic cysts are common lesions with different biological behavior. Odontogenic keratocysts (OKCs) and calcifying odontogenic cysts (COCs) with ameloblastoma-like epithelium are more aggressive than dentigerous cysts (DCs) and radicular cysts (RCs). Therefore, they were included in the list of odontogenic tumors by WHO. Osteopontin (OPN) is a calcium-binding glycoprotein present in many normal tissues. It plays a role in the migration and invasion of transformed epithelial cells. Binding of OPN to its receptor CD44v6 can enhance cell motility and migration. The purpose of this study was to compare the expression of these markers between odontogenic cysts of varying biological behavior. We examined OPN and CD44v6 expression in tissue sections of 14OKCs, 14COCs, 14RCs and 14DCs by immunohistochemistry. OPN and CD44v6 immunostaining was observed in all lining epithelial cells of the studied lesions with different degrees. The highest level of OPN and CD44v6 expression was found in OKCs, followed by COCs, RCs and DCs. Comparison of both markers among four groups revealed significant differences (P<0.001). Our findings suggest that higher level of OPN and CD44v6 expression in epithelial cells of some lesions such as OKC and COC can explain the local aggressive behavior of them.     

Genotypic profiles and virulence attributes of Candida albicans isolates from patients with oral lichen planus

Candida albicans carriage has been found to be increased in patients with oral lichen planus. In the present work we have investigated the genotypic profiles of 112 C. albicans strains isolated from patients with erosive or nonerosive OLP, and from healthy controls. The virulence attributes of the isolated strains were compared to elucidate the pathogenetic mechanisms through which C. albicans may cause OLP. We have characterized the genotypic profiles of these isolated strains using a randomly amplified polymorphic DNA assay. In addition, we used assays to measure adhesion to buccal epithelial cells and phospholipase activity to evaluate the virulence attributes of these isolates. Our RAPD analyses revealed four different genotypes, named type A to D, among all isolates, and identified statistically significant associations with disease conditions. Specifically, type A (58.1%) and C (29.0%) were primarily found in erosive OLP, while type A (33.3%) and D (58.3%) were identified in nonerosive OLP. However, the healthy group seemed to have type B (38.5%) and D (61.5%). Using adhesion to BEC assay, we demonstrated that the isolates with genotype A had the strongest adherence among the four genotypes (P=0.000<0.05). The phospholipase activity of the isolates with genotype A and C was higher than for those with genotype B and D (P=0.000<0.05). In conclusion, some C. albicans isolates with special genotypic profiles and virulence attributes may contribute to the pathogenesis of OLP.     

Expression of the FUT2 gene and CD44 marker in patients with oral lesions

The aim of this work was to investigate the FUT 2 gene, the secretor status and the expression of CD44 protein in epithelial cells obtain from saliva samples from patients with oral lesions (benign, pre-cancerous and cancerous lesions, n = 94). We analyzed polymorphisms of the FUT2 gene by allele specific oligonucleotide–polymerase chain reaction. The FUT2 gene encodes the α(1,2) fucosyltransferase (Se enzyme) that regulates the expression of ABH antigens in secretions. Generally speaking, being a non-secretor has several disadvantages with regard to metabolism and immune function. In this study, we found that oral pre-cancerous and cancerous lesions were increased among individuals with non-secretor status and nonsense mutation 428G→A. Fifty-one percent of the patients with oral pre-malignant and malignant lesions were non-secretors, in contrast with the healthy population (OR = 3.44). We observed a marginal association between secretor status and these lesions. Our study suggests that the lack of wild type FUT2 gene and a non-secretor status appear to be an associated risk marker for the development of oral cancer in patients with oral lesions.     

Palmitoylation of CD44 interferes with CD3-mediated signaling in human T lymphocytes

We studied the interactions between CD44 and four differentmonoclonal antl-CD44 antibodies. All four monoclonal anti-CD44antibodies studied (P3H9, Bu52, IM.7, and GKW.A3) act in synergywith human anti-CD2 antibodies in stimulating normal human peripheralblood lymphocytes to proliferate. GKW.A3 and IM.7 but not P3H9or Bu52 Inhibited the proliferation of normal human peripheralblood lymphocytes stimulated by antl-CD3. Interestingly, onlyGKW.A3 and IM.7 stimulated the incorporation of [3H]palmltlcacid and palmitoylation of CD44 molecules by normal human peripheralblood lymphocytes. The two monoclonal antl-CD44 antibodies (P3H9and Bu52) that failed to inhibit antl-CD3 induced proliferationalso failed to induce the incorporation of [³H]palmltlc acid.More Importantly, the inhibitory effects of GKW.A3 were reversedin the presence of cerulenln, an inhibitor of protein palmitoylation.Therefore, palmitoylation of CD44 may interfere with antl-CD3mediated signaling pathways. These data support the hypothesisthat palmitoylation of cell surface receptors may play an activerole in receptor and receptor interactions and signal transductlonin normal human T lymphocytes.     

凋亡抑制蛋白c-FLIP在扁平苔癣患者外周血淋巴细胞和皮损中的表达

目的 探讨凋亡抑制蛋白c-FLIP(细胞型Fas相关死亡区域蛋白样IL-1β转换酶抑制蛋白)在扁平苔癣患者外周血和皮损中的表达和分布情况.方法 采用流式细胞仪检测30例扁平苔癣患者和20例正常人对照组外周血T细胞内c-FLIP表达阳性率,采用免疫组化方法 检测c-FLIP在其皮损中的表达.结果 扁平苔癣患者外周血T细胞c-FLIP表达(6.32%±1.17%)明显高于正常人对照组(2.28%±0.54%),P<0.05.而两组在外周血B细胞内的表达分别为0.78%±0.16%和0.69%±0.18%,差异无统计学意义(P>0.05).c-FLTP蛋白在扁平苔癣患者皮损中的表达(89.73%±5.24%)明显高于正常人对照组(121.58%±7.93%),P<0.01.结论 凋亡抑制蛋白c-FLIP在扁平苔癣患者的外周血T细胞和皮损内明显高表达,可能参与扁平苔癣患者T细胞的增殖.     

Characterization of CD44 expressed on alveolar macrophages in patients with diffuse panbronchiolitis.

Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with diffuse panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low(+)) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB.     

Expression in vivo of CD45RA,CD45RB and CD44 on T cell receptor-transgenic CD8+ T cells following immunization

We used mice transgenic for a major histocompatibility complex class I-restricted T cell receptor to study the changes of phenotype in vivo which follow priming by antigen of CD8 T cells. We show that following priming with peptide, CD44 on CD8 T cells is up-regulated. The change of phenotype was relatively stable, as primed CD8 cells isolated from thymectomized mice 6 weeks after priming still expressed increased levels of CD44. CD8 T cells in these mice are still responsive to peptide and could represent long-lived primed cells. No downregulation in vivo of the CD45RA or CD45RB isoforms was found, indicating that there is a differential regulation of the expression of CD44 and CD45RB by activated CD8 transgenic T cells. These results contradict earlier studies in vitro which showed that CD8 T cells which have been primed earlier belong to the CD45RA^? or CD45RB^? subset.