A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells in an early stage of pregnancy

The decidua is the place where the fertilized egg is implanted and where the immunocompetent cells of the mother come into direct contact with genetically disparate cells of the conceptus. Although the T cells in the decidua are exposed to fetal antigens, the fetus is not rejected by maternal immunocompetent cells. In the present study, we examined surface markers to determine whether the T cells in the human decidua are naive T cells without or memory T cells with a history of antigen stimulation. Although few T cells were present in the decidua, as compared to the peripheral blood, CD45RO⁺, CD29⁺ and CD45RA⁻ CD4⁺ T cells as well as CD45RO⁻, CD29⁺ and CD45RA⁻ CD8⁺ T cells, which are considered to be memory T cells, were in the majority, with only small numbers of CD45RO⁻, CD29⁻ and CD45RA⁺ CD4⁺ and CD8⁺ cells, which are naive T cells, present. Also, the decidual mononuclear cells secreted IL-2 and IL-4. Since IL-4 is secreted only by memory T cells, it is suggested that in the decidua memory T cells increase in number and secrete cytokines, thereby in some way influencing the phenomenon of fertility.     

CD50 and CD62L adhesion receptor expression on naive (CD45RA+) and memory (CD45RO+) T lymphocytes in the elderly.

A complex reshaping characterizes cellular immunity in the elderly. In particular, the hallmark of the "senescence" of the T cell compartment is a decrease in the proportion of CD45RA+ naive T lymphocytes concomitantly with an expansion of CD45RO+ memory T cells. However, in addition to age-dependent changes in their representation, phenotypical and functional anomalies also characterize naive and memory T cell populations in the elderly. Since cell adhesion molecules (CAMs) are multifunctional receptors which play important roles not only in cell-to-cell and cell-to-matrix interactions but also in signal transduction and cell activation, we analysed, by means of a three-colour flow cytometry method, the proportion, absolute number and density expression or mean fluorescence intensity (MFI) of CD50 (ICAM-3) and CD62L (L-selectin homing receptor) adhesion receptors on CD45RA+ and CD45RO+ peripheral blood CD3+ T cell subsets from 10 healthy elderly subjects and 10 young controls. Our aim was to investigate age-dependent changes in the expression pattern of these CAMs on naive and memory lymphocytes which might contribute to the remodelling of the immune system in the elderly. We considered the mean values +/- standard deviations of the percentage, absolute number and MFI of positive cells. The percentage of naive T cells expressing CD50 was not significantly modified in aged (94.8 +/- 5.0%) compared to young individuals (97.8 +/- 3.2%). On the contrary, the percentage of memory T cells exhibiting CD50 was lower in elderly than young donors (92.0 +/- 6.4 vs. 98.3 +/- 2.2%; p < 0.01). The percentage of naive T cells expressing CD62L was decreased in the elderly donors (53.3 +/- 18.8 vs. 80.8 +/- 11.0%; p < 0.001), whereas the proportion of CD62L+ memory T lymphocytes was substantially comparable between the two age groups (63.5 +/- 15.7 vs. 54.7 +/- 12.3%). The absolute number per mm(3) of CD50+ naive T cells from aged individuals was decreased (251.9 +/- 141.9 vs. 621.8 +/- 238.0/mm(3); p < 0.001), whereas memory peripheral blood T lymphocytes expressing CD50 were substantially unchanged (863.8 +/- 260.9 vs. 802.7 +/- 139.6/mm(3)). On the contrary, the absolute numbers per mm(3) of naive and memory peripheral blood T lymphocytes exhibiting CD62L were respectively decreased (190.8 +/- 133.4/mm(3)) and increased (515.1 +/- 146.8/mm(3)) in elderly donors compared to young controls (601.3 +/- 129.1 and 351.8 +/- 195.0/mm(3); p < 0.001 and p < 0.05, respectively). Finally, CD50 MFI values of naive as well as memory T cell subpopulations from aged subjects were increased compared to young donors (14.0 +/- 2.0 vs. 9.8 +/- 1.2 and 14.0 +/- 2.0 vs. 11.6 +/- 1.3; p < 0.001 and p < 0.01, respectively). CD62L was also overexpressed in both naive (8.4 +/- 1.6 vs. 6.7 +/- 1.4; p < 0.05) and memory (10.3 +/- 2.5 vs. 5.4 +/- 1.1; p < 0.001) T subsets in the elderly. CD50 and CD62L upregulation could be interpreted as a compensatory mechanism for a decreased responsiveness and a greater requirement for activation signals rather than an age-related anomaly.     

Loss of activation-induced CD45RO with maintenance of CD45RA expression during prolonged culture of T cells and NK cells.

The results of the present study show that activation-induced changes in CD45RA and CD45RO expression on T cells and natural killer (NK) cells are not unidirectional for all cells during a 5-week culture period. T cells and NK cells were generated from a resting subpopulation of peripheral blood mononuclear cells (PBMC) defined by sedimentation at Percoll high buoyant densities (p greater than 1.0640 g/ml) and unresponsiveness to IL-2. T cells were activated by a combination of PHA, sheep erythrocytes and IL-2-conditioned medium (IL-2-CM), and NK cells were activated by co-culture with gamma-irradiated malignant melanoma (MM-170) cells and IL-2-CM. Both T-cell and NK-cell cultures were maintained by subculture in IL-2-CM. NK cells and the CD45R(Abright)RO(dim/neg) subpopulation of T cells gained CD45RO following activation and this was accompanied by a two-fold decrease in CD45RA expression. In different cultures, CD45RO expression was not stable on 28-80% of T cells and 10-55% of NK cells. Cells with decreased CD45RO expression showed increased expression of CD45RA. Instability of CD45RO expression on cultured T cells and NK cells occurred at a time following the period of rapid cell growth when the cells were entering a quiescent phase. Both the CD4+ and CD8+ T-cell subpopulation showed similar changes in CD45 isoform expression. In contrast to the results obtained with the CD45R(Abright)RO(dim/neg) resting T cells, the CD45RO(bright)RA(dim/neg) subpopulation of resting T cells when activated and cultured under identical conditions retained CD45RO expression and remained CD45RAdim/neg. Thus a significant proportion of resting CD45R(Abright)RO(dim/neg) T cells is not related in a differentiation sequence to resting CD45RObrightRAdim/neg T cells, and therefore resting CD45RAbrightROdim/neg T cells and resting NK cells may be heterogeneous with respect to their activation history.     

Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection.

Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8+ and CD4+ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double-labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4+ CD45RA+, CD4+ CD45RO+, CD8+ CD45RA+, and CD8+-CD45RO+. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4+ CD45RA+ cells (median = 5.0 cells/HPF) relative to CD4+ CD45RO+ (3.12 cells/HPF), CD8+ CD45RA+ (2.14 cells/HPF), and especially CD8+ CD45RO+ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4+ CD45RA+ cells (6.67 cells/HPF, P < 0.09) and the greatest for CD8+ CD45RO+ cells (7.00 cells/HPF, P < 0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO+ to CD45RA+ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P < 0.008) and CD8 (1.43 versus 0.58, respectively; P < 0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA+ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO+ T cells, especially in the CD8 population.     

Lymphokine gene expression related to CD4 T cell subset (CD45R/CDw29) phenotype conversion

In this study, we investigated whether the phenotype-related differentiation of human 2H4+ (CD45R) naive cells to 2H4- (CDw29) memory CD4 cells corresponded to modulation of interleukin (IL) 2, IL 4, interferon (IFN)-gamma and granulocyte-monocyte colony-stimulating factor (GM-CSF) gene expression, a phenomenon which might correlate to the distinct functional activities of naive cells or memory cells. To mimic in vitro CD4 T cell subset differentiation, freshly isolated 2H4+ and 2H4- CD4 cells were stimulated with the anti-CD3 antibody (Leu-4), expanded in IL 2-containing medium and restimulated with Leu-4 after 7 and 13 days. Absence of monocyte-T cell interaction was compensated by adding monocyte supernatant to the culture medium and by cross-linking the anti-CD3 antibodies with goat anti-mouse antibody coated on culture dishes. It has been previously shown that in vitro stimulated 2H4+ cells acquire CDw29 surface antigens. Measurement of lymphokine gene expression by dot-blot hybridization revealed that although stimulated 2H4+ cells proliferated less than stimulated 2H4- cells, and expressed less actin mRNA, they expressed more IL 2 but less IL 4 and GM-CSF than 2H4- cells. No significant difference was observed between the two subsets for the expression of IFN-gamma. If subsets were restimulated with Leu-4 antibodies, expression of IL 2 was decreased and expression of IL 4 was increased in both subsets; however, the differences among the subsets persisted. They were even more enhanced for IL 2 but less pronounced for GM-CSF. Thus, in spite of phenotype conversion, CD4 T cell subsets maintained a distinct capacity to express IL 2 and IL 4 genes.     

Studies of lymphocyte transendothelial migration: analysis of migrated cell phenotypes with regard to CD31 (PECAM-1), CD45RA and CD45RO.

CD31 is a 130,000 MW cell-surface glycoprotein expressed on endothelial cells, polymorphonuclear leucocytes, monocytes and about 50% of peripheral blood lymphocytes, and it has been proposed that it plays a role in transendothelial migration. If it is involved in endothelial transmigration of lymphocytes then the proportion of CD31+ cells should be increased in the lymphocyte population which has crossed an endothelial monolayer. This was tested using two endothelial types, namely human umbilical vein endothelial cells (HUVEC) and rat high endothelial venule (RHEV) cells. As a control, lymphocyte CD45RA and CD45RO expression was also determined since there is a correlation between lymphocytes bearing these isoforms and different migratory patterns. Double labelling techniques showed a close correlation between CD31 and CD45RA expression. With HUVEC monolayers, the transmigrated lymphocyte population was depleted of CD31+ cells. This depletion was even more marked if the HUVEC monolayers had been stimulated with interleukin-1 beta (IL-1 beta). The migrated lymphocytes were enriched for CD31-CD45RO+ cells but depleted of CD31+CD45RA+ cells. In addition, lymphocyte populations depleted of CD31+ cells by immunopanning were also able to migrate across HUVEC monolayers. Taken together these data suggest that lymphocyte CD31 expression is not necessary for transmigration across HUVEC monolayers and, if anything, is negatively correlated with transmigration. With the second endothelial cell type, RHEV cells, there was no consistent change in the proportion of CD31+ lymphocyte in the transmigrated population, suggesting neither a positive nor a negative correlation between CD31+ expression and lymphocyte transmigration across RHEV cells. However, with both endothelial cell types, the migrated lymphocyte populations were enriched for the marker CD45RO. In conclusion, lymphocyte surface expression of CD31 is not necessary for transmigration across the endothelial cell types used in this study, but with both cell types an enrichment of CD45RO+ lymphocytes is seen in the migrated population.     

Biochemical association of CD45 with the T cell receptor complex: regulation by CD45 isoform and during T cell activation.

CD45 is the predominant transmembrane tyrosine phosphatase in lymphocytes and is required for the efficient induction of T cell receptor signaling and activation. However, the regulation of CD45 activity and substrate specificity are poorly understood. In the present study, we demonstrate a basal biochemical association of CD45 with the T cell receptor complex that is regulated in part by CD45 isoform expression. Further, maintenance of CD45/TCR association is differentially regulated following TCR ligation with peptide: a partial agonist peptide induces CD45/TCR dissociation while an agonist peptide promotes sustained association in a CD4-dependent manner. These data suggest that T cell receptor signaling pathways may be modulated by altering access of CD45 to TCR-associated substrates involved in T cell activation.     

Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes

Cryostat sections of histologically normal human colon were studied by double-label immunofluorescence techniques using a panel of monoclonal antibodies to T-lineage antigens and activation markers, with particular reference to the CD6 antigen. In the lamina propria, the majority population of T cells was of the CD3+, CD6+, CD4+ subset, of which virtually all were of the UCHL1+, CD45R-, Leu 8- phenotype of antigen-committed helper T cells. This majority lamina propria population did not express markers associated with blastogenesis (CD7), activation (MHC class II, CD25, CD38) or proliferation (OKT9, Ki67). In both intra-epithelial and lamina propria compartments, a subpopulation of CD3+ T cells was identified which did not express either the CD6 or CD5 peripheral 'pan T' markers. Most of the CD3+, CD6- cells were of the CD8+ (cytotoxic-suppressor) subset which co-expressed the CD7 antigen with a much higher frequency than did the CD6+ subpopulation. Expression of CD25, CD38 and HLA-D antigens, although infrequent, was confined to this CD8+, CD5-, CD6- population. Our data thus imply that the colonic mucosa is largely populated by mature, antigen-committed resting T cells of the helper-inducer phenotype.     

Human CD4+ T cells expressing CD45RA acquire the lymphokine gene expression of CD45RO+ T-helper cells after activation in vitro.

CD4+ T cells were separated into subpopulations according to their expression of different isoforms of the CD45R molecule, i.e. CD45RA and CD45RO. The separated cells were activated with staphylococcal enterotoxin A (SEA) in the presence of formalin fixed Raji cells. Each set of cells was activated twice with a 6-day interval, and the lymphokine gene expression during the first 3 days after initiation of each stimulation was followed by use of polymerase chain reaction (PCR) technology. The lymphokine messenger RNA (mRNA) profiles were found to differ between the subsets, since after the first stimulation the CD45RA+ cells produced mRNA encoding interleukin-2 (IL-2) and IL-1 alpha, whereas the CD45RO+ cells transcribed genes for IL-1 alpha, IL-2, IL-4, IL-5 and interferon-gamma (IFN-gamma). After 6 days of SEA stimulation both populations were mainly CD45RO reactive, and when restimulated displayed the lymphokine mRNA profile restricted to this subset. These results indicate that the CD45RA subset is a precursor of the CD45RO and further strengthen the hypothesis that the former cell population represents naive whereas the latter subset represents memory T cells within the CD4 subset.     

Deficiency of the expression of CD45RA isoform of CD45 common leukocyte antigen in CD4+ T lymphocytes in children with infantile cholestasis

The immunological background of the pathological changes that appear in infantile cholestasis (infections, inflammatory process in the liver) is largely unknown. With the use of double color flow cytometry, we assessed the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 29 infants with extra and intra-hepatic cholestasis (12 and 17 patients, respectively), aged from 1 to 8.6 months. Control group consisted of 15 age-matched, healthy infants. We examined: (1) the expression of CD3, CD4, CD8, CD19 lymphocyte surface receptors; and (2) the distribution of lymphocyte subsets with distinctive surface Ag characteristics of 'naive' (CD45RA+) and 'memory' (CD45RO+) cells in both CD4+ and CD8+ cell populations. The surface markers expression was evaluated in terms of percentage of positive cells and receptor density. The following changes in the expression of lymphocyte surface markers are described: (1) a decrease in the percentage of total CD3+, CD4+ cells but normal percentage of CD8+ cells and elevated proportion of CD19+ B cells; (2) a reduction of the proportion of 'naive' CD4+ lymphocytes but normal percentage of 'naive' CD8+ as well as 'memory' CD4+ and CD8+ cell subsets; (3) a decrease in density of CD3, CD4+, CD8 receptors, and D45RA isoform in a subset of 'naive' CD4+ cells. We conclude that deficiency of 'naive' CD4+ T cell subset which possess important effector and immunoregulatory functions, and low expression of certain lymphocyte receptors known to be engaged in T cell activation, possibly reflect a defect of cell mediated immunity that may account for viral and bacterial infections, often observed in infants with cholestasis.     

Expression of naive/memory (CD45RA/CD45RO) markers by peripheral blood CD4+ and CD8+ T cells in children with asthma

Introduction: The role of CD4⁺ T cells in the immunopathogenesis of asthma is well documented. Little is known about the role of CD8⁺ T cells. The aim of this study was to assess peripheral blood subsets of CD4⁺ and CD8⁺ T cells expressing naive/memory markers (CD45RA⁺/RO⁺) and the activation marker (CD25⁺) in children with allergic asthma. Materials and Methods: Peripheral blood mononuclear cells were isolated from children with allergic asthma and healthy children. T cell subsets were analyzed by flow cytometry for the expressions of CD45RA, CD45RO, and CD25. In this study, some differences in the memory compartment of peripheral blood T cells between asthmatic children and healthy controls were detected. Results: The absolute number of CD8⁺ T cells expressing CD45RO was significantly elevated and the percentages of CD3⁺ T cells expressing activation marker CD25 and of CD4⁺ T cells expressing memory marker CD45RO were significantly lower in children with asthma compared with controls. No correlation was found between severity of asthma and peripheral blood lymphocyte subsets. Conclusions: There were some differences in the memory compartment of peripheral blood T cells between asthmatic children and healthy controls. The increase in the number of CD8⁺ T cells expressing the memory marker (CD45RO) in children with allergic asthma may indicate that CD8⁺ T cells play a role in the pathogenesis of asthma.     

Evidence for differential expression of CD45 isoforms by precursors for memory-dependent and independent cytotoxic responses: human CD8 memory CTLp selectively express CD45RO (UCHL1)

On the basis of differential CD45 expression, human T cells can be separated into approximately reciprocal populations. The mAb UCHL1 detects a 180 kd molecular mass isoform, CD45R0. The CD45RA cluster of mAbs reacts with CD45 isoforms of 205 and 220 kd molecular mass. These reagents subdivide both CD4 and CD8 T cell populations. CD4 T cells that proliferate in response to memory-dependent (recall) antigens have been shown to selectively express CD45R0. We extend these observations to a model for cytotoxic responses that allows the functional analysis of CD8 T cells with differential CD45 expression. Precursors for allo-specific CTL responses are readily detectable in CD45R0 as well as CD45RA populations. In contrast, we find memory CTLp greatly enriched among CD45R0 cells. In combination with earlier work, these results suggest that differential expression of CD45 isoforms is associated with memory formation for different classes of immune responses in both major T cell lineages.     

Functional analysis of human T cell subsets defined by CD45 isoform expression.

The properties of human CD45RA and CD45RO T cells are described. CD45RO cells respond to recall antigens and provide help for B lymphocytes. They produce a wide variety of cytokines including IL-2, IL-4 and IFN-gamma. CD45RA T cells respond poorly to recall antigens and produce mainly IL-2. The phenotype of CD45RO cells suggests that they may be in cycle and in vivo data shows that they have a short lifespan while CD45RA cells are long-lived. The lineage relationship of the two subsets is not clear but in vivo and in vitro evidence suggests bi-directional conversion between CD45RA and CD45RO phenotypes.     

Inhibitory effect of IL-4 on the sepharose-CD3-induced proliferation of the CD4CD45RO human T cell subset

CD45R monoclonal antibodies are able to distinguish two different subsets of the CD4 human T cells. This phenotypic split is accompanied by functional diversity. In this report we have analyzed the capabilities of CD45R subsets of CD4 human T cells to use interleukin 2 (IL-2) and IL-4 as growth factors. We have found that both cell subsets are able to proliferate after stimulation with Sepharose-CD3 in the presence of externally added IL-2 or IL-4. However, the response to IL-4 of CD4CD45RO cells was comparatively lower than the response of CD4CD45RA cells. Both cell subsets showed a good response to Sepharose-CD3 plus adherent cells (AC), but when IL-4 was present in the culture only the CD4CD45RA cells showed an enhancement in the Sepharose-CD3-induced proliferation, while proliferation of the CD4CD45RO T cell subset was inhibited. Similar effects were seen, however, in the response to CD4CD45RA or CD4CD45RO cells to Sepharose-CD3 plus IL-2. Although the precise mechanism of the inhibitory effect of IL-4 is not known, the results obtained suggest that IL-4 could interfere in some way with the signalling of IL-2 to the proliferation of the CD4CD45RO T cell subset.     

Interaction between the CD45 antigen and phytohemagglutinin. Inhibitory effect on the lectin-induced T cell proliferation by anti-CD45 monoclonal antibody

Immunoprecipitation studies from 125I-labeled T cells, previously activated with the lectin phytohemagglutinin (PHA) from Phaseolus vulgaris, showed a preferential association between the CD45 glycoprotein family containing members of 220, 205, 190 and 180 kDa, and a protein of 33 kDa. This 33-kDa protein, with an identical molecular mass as PHA, was not associated with other highly expressed molecules such as class I histocompatibility antigens (HLA-A,B,C), transferrin receptor, CDw44 and CD11a. Further immunoprecipitation analysis from peripheral blood lymphocytes incubated with 125I-labeled PHA confirmed the identification of the CD45-associated 33-kDa protein as the lectin PHA. These results prompted us to analyze the possible involvement of the CD45 molecules in the T cell activation process induced by PHA. Thus, two monoclonal antibodies specific for CD45 antigens were able to inhibit the T cell proliferation induced by the lectin. This inhibitory ability was exerted by affecting both the interleukin 2 production and the interleukin 2 receptor expression.     

Biochemical and functional characterization of the leucocyte tyrosine phosphatase CD45 (CD45RO, 180 kD) from human neutrophils. In vivo upregulation of CD45RO plasma membrane expression on patients undergoing haemodialysis.

The biochemical and functional characterization, and the regulation of plasma membrane expression of the leucocyte tyrosine phosphatase CD45, have been investigated in neutrophils from healthy donors and patients undergoing haemodialysis. CD45 proteins of 180 kD and 130-150 kD were precipitated from neutrophils from both healthy subjects and haemodialysed patients. Prolonged storing, as well as trypsin treatment of samples containing the 180-kD CD45 protein, generated the 130-150-kD polypeptides. The 130-150-kD CD45 polypeptides carried extracellular CD45 epitopes, including the sialic acid-related UCHL1 epitope (CD45RO). Furthermore, these trypsin-generated CD45 polypeptides did not possess phosphatase activity, which could be detected on the 180-kD protein. A remarkable quantitative increase of cell surface expression of the neutrophil CD45 components was detected both after in vitro neutrophil activation and after dialysis treatment with neutropenic membranes. The CD45 biochemical pattern did not qualitatively change upon either in vitro or in vivo dialysis-induced neutrophil activation. The upregulated expression of CD45 on neutrophils from dialysed patients correlated with the neutropenic effect induced by the different dialyser membranes. Maximal upregulation of CD45 expression was observed after 15 min of dialysis with neutropenic membranes, and normal expression levels were restored after 1 h. By contrast, increase of CD45 plasma membrane expression induced in vitro by treatment of normal neutrophils with the degranulatory agents fMLP or Ca2+ ionophore was maintained. These results demonstrate that neutrophil cell surface expression of the 180-kD CD45 protein is upregulated during the in vivo haemodialysis process, and suggest that a proteolytic activity could regulate the enzymatic activity of CD45 by degranulation of its cytoplasmic phosphatase domains.     

桥本氏甲状腺炎患者外周血中CD4+ CD45RO+ 记忆性T 细胞的表达及意义

目的:检测初诊桥本氏甲状腺炎(Hashimoto’s thyroiditis,HT)患者外周血CD4+ CD45RO+ 记忆性T 细胞比例,探讨其在HT 发病中的意义。方法:收集初诊的HT 患者作为病例组(HT,n =53),另外选取年龄、性别相匹配的正常人作为对照组(HC,n =43),并根据甲状腺功能状态将HT 组分为甲状腺功能正常组(HT-A,n =15)、亚临床甲减组(HT-B,n =14)和临床甲减组(HT-C,n =24)。流式细胞仪检测外周静脉血中CD4+ CD45RO+记忆性T 细胞比例,酶联免疫吸附法检测血清中IFN 、IL-17 水平,化学发光法检测甲状腺功能及甲状腺特异性抗体滴度。结果:HT 组外周血中CD4+ CD45RO+ 记忆性T 细胞比例、IFN 、IL-17、TPOAb 与TgAb 水平均显著高于HC 组,P<0.01。双变量相关分析显示HT 患者外周血CD4+ CD45RO+记忆性T 细胞的比例与IFN 、TPOAb、TgAb 均呈正相关(P<0.01,P =0.015,P<0.01)。结论:CD4+ CD45RO+ 记忆性T 细胞在HT 患者外周血中呈高表达,CD4+ CD45RO+记忆性T 细胞可能参与了HT 的发病过程。     

Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients.

A comprehensive peripheral blood immunophenotype analysis of 16 multiple sclerosis (MS) patients was performed by three-color flow cytometric analysis, and the results were compared with those for age-matched healthy controls. The cell subsets quantified included T cells (CD3+), B cells (CD19+), NK cells (CD56+), CD4+ and CD8+ T cells, cytotoxic (CD28+) and suppressor precursor (CD28-) CD8+ T cells, CD45RA+ and CD45RO+ T cells (CD4+ and CD8+), and CD5+ T and B cells. Analysis of MS patients' peripheral blood revealed essentially normal levels of total T, B, and NK cells. In agreement with results obtained by other investigators, it was found that MS patients had an increased CD4/CD8 ratio, primarily due to a decrease in CD8+ T cells. MS patients were found to have a significantly decreased level of suppressor precursor (CD28-) CD8+ T cells compared with that of controls but to have normal levels of cytotoxic (CD28+) CD8+ T cells. These data indicate that MS patients do not have a general decrease in CD8+ T cells but that they have a specific decrease in the suppressor precursor subset only and normal levels of cytotoxic CD8+ T cells. MS patients also had a significant increase in memory (CD45RO+) CD4+ T cells and displayed a trend towards a decrease in naive (CD45RA+) T cells in the peripheral blood.     

Increased CD45RO expression on T lymphocytes in mediastinal lymph node and pulmonary lesions of patients with pulmonary sarcoidosis.

Sarcoidosis is characterized by a cell-mediated response mediated by the activation of CD4+ T lymphocytes in an environment lacking adequate numbers of regulatory CD8+ T lymphocytes. Immunohistological studies on frozen tissues have shown that sarcoid lesions have activated CD4 helper/inducer T lymphocytes at the centre of granulomata, whereas lymphocytes at the periphery are mainly CD8 suppressor/cytotoxic cells. In this study we investigated the immunohistological distribution of CD45 isoforms of T cells in 29 paraffin-embedded sarcoid lesions in mediastinal and open lung biopsies. Ten of these were assessed quantitatively, with single-staining of serial sections demonstrating a predominance of CD45RO memory T lymphocytes in granulomata and intergranulomatous areas. Ratios of CD45RO:CD45RA T lymphocytes (or the ratio of memory to naive T cells) were 42.0:1 for granulomata and 17.9:1 for intergranulomatous areas of sarcoid lesions counted. This finding is compatible with the hypothesis that nearly all the lymphocytes present in sarcoid lesions have been previously activated, and selectively home to sarcoid lesions.