老年社区获得性肺炎并脓毒症患者sCD14和CD14+/HLA-DR表达及意义

目的 探讨老年社区获得性肺炎（CAP）并脓毒症患者血清sCD14和外周血单核细胞CD14+/HLA-DR表达水平及临床意义。方法 选取2015年1月~2018年12月我院呼吸内科及ICU收治的老年CAP患者126例,根据是否并发脓毒症将老年CAP患者分为脓毒症组56例,非脓毒症组70例,另选择老年健康体检者45例为对照组,脓毒症组根据是否存活分为死亡组30例及存活组26例。采用ELISA法和流式细胞术检测并比较各组血清sCD14及外周血单核细胞CD14+/HLA-DR+表达水平,脓毒症组及非脓毒症组48 h CURB-65评分、28 d死亡率。结果 脓毒症组血清sCD14水平高于非脓毒症组和对照组,而CD14+/HLA-DR+表达水平则低于非脓毒症组和对照组,差异均有统计学意义（P＜0.05）。死亡组血清sCD14水平高于存活组,CD14+/HLA-DR表达水平低于死亡组,差异有统计学意义（P＜0.05）;相关分析显示,血清sCD14水平与CURB-65评分和28 d死亡率呈正相关（r=0.750、0.712,P＜0.05）,而与CD14+/HLA-DR呈负相关（r=-0.692,P＜0.05）,CD14+/HLA-DR与CURB-65评分和28 d死亡率呈负相关（r=-0.653、-0.721,P＜0.05）。结论 老年社区获得性肺炎并脓毒症患者存在免疫失衡,血清sCD14和CD14+/HLA-DR表达水平与CURB-65评分和28 d死亡率密切相关,可作为早期预测感染性疾病病情严重程度和预后的免疫学指标。     

Reduced frequencies of peripheral interferon-gamma-producing CD4+ and CD4- cells during acute Kawasaki disease

BACKGROUND: This study was performed to analyze the frequencies of peripheral interferon (IFN)-gamma-producing cells at the single-cell level and to determine concentrations of circulating IFN-gamma in the acute and subacute phases of Kawasaki disease (KD). METHODS: Ten patients with KD were studied and seven healthy children were selected as control subjects. Using immunofluorescent detection of intracellular IFN-gamma in CD4-positive and CD4-negative cells, the frequencies of IFN-gamma-producing cells in peripheral blood mononuclear cells were studied. Circulating IFN-gamma levels were measured by enzyme-linked immunosorbent assay. RESULTS: The frequencies of peripheral blood CD4+ and CD4- IFN-gamma-producing cells in acute-phase KD patients were significantly lower than in subacute-phase KD patients and control children (p < 0.05). CD4- cells, thought to be mainly composed of CD8+ cells, appeared to be more responsible for the reduced frequencies of total IFN-gamma-producing cells than CD4+ cells. There were, however, no differences in the frequencies of IFN-gamma-producing cells between KD patients in the subacute phase and control children. In contrast, serum IFN-gamma levels were higher in KD patients in the acute phase than in the subacute phase (p < 0.05). CONCLUSIONS: The above results show increased levels of circulating IFN-gamma and decreased emergence of peripheral IFN-gamma-producing cells in acute KD patients, suggesting transient infiltration of activated IFN-gamma-producing cells into the inflammatory sites during acute KD. These findings also support the hypothesis that IFN-gamma plays an important role in the pathogenesis of KD-related vasculitis.     

Elevation of soluble CD23 in sera from patients with infectious mononucleosis

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM. J. Med. Virol. 53:384–387, 1997. © 1997 Wiley-Liss, Inc.     

Myeloid and lymphoid activation markers in AIDS and non-AIDS presenters

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Myeloid dendritic cell (mDC), plasmacytoid dendritic cell (pDC), slanDC, monocyte and T-lymphocyte cell counts and activation status, were assessed by flow cytometry in peripheral blood samples. Soluble (s)CD14 and sCD163 were assessed in plasma samples using ELISA assays. Statistical analyses were performed using GraphPad Prism and Minitab Express.Thirty-four ART naïve HIV-1 infected subjects were enrolled in this study (22 non-AIDS and 12 AIDS presenters). Seventeen healthy donors (HD) were included as control group. Although circulating mDC levels resulted unchanged, HLA-DR expression was decreased on mDCs of HIV positive subjects compared to HD (p?<?0,0001). AIDS presenters showed the lowest level of expression of HLA-DR on mDCs. Circulating levels of pDCs were decreased in HIV patients compared to HD (p?<?0,001), without any changes in HLA-DR expression. SlanDC cell counts were extremely reduced in AIDS presenters, compared to non-AIDS presenters and HD (p?<?0,01 and p?<?0,0001, respectively) and showed higher HLA-DR expression in HIV patients compared to HD (p?<?0,01). Intermediate monocyte (IM) cell counts were increased in AIDS and non-AIDS presenters compared to HD (p?<?0,001 and p?<?0,001 respectively). Furthermore, IM expansion was directly correlated to HIV viral load (p?=?0,036) and independent from CD4 cell counts and activation levels. Plasma concentrations of sCD14 and sCD163 resulted increased in HIV infected subjects compared to HD (p?<?0,0001 and p?<?0,001), with the highest levels observed in AIDS presenters. After 1?year, ART was able to increase pDC and decrease IM absolute cell counts and modify HLA-DR expression on mDCs and slanDCs, approaching the levels observed in HD. ART reduced also CD4 and CD8 activation levels. In conclusion, in untreated HIV infected subjects circulating dendritic cells resulted altered either in numbers or in HLA-DR expression, especially in AIDS presenters. IM absolute counts were equally increased in AIDS and non-AIDS presenters. ART was able to reduce myeloid and lymphoid inflammation in both advanced and non-advanced HIV patients, confirming the role of ART in hampering disease progression and immune activation associated non-AIDS events.     

Expression of activation, adhesion molecules and intracellular cytokines in acute pancreatitis.

Adhesion and activation molecules as well as cytokines play an important role in an immune scenario. In acute pancreatitis, we have studied some of these in order to evaluate dysregulation. For this we took peripheral blood mononuclear cells and pancreatitis tissue cells. We analysed activation markers like CD69, CD25 and HLA-DR and found a marked elevation of CD69 as well as CD25 in both peripheral blood cells and tissue mononuclear cells when compared to controls. In PBMC-CD69: P<0.01 and CD25: P<0.01; in tissue-CD69: P<0.001 and CD25: P<0.001. The HLA-DR levels, however, were reduced in the disease state (in acute pancreatitis patient blood (P<0.01) and tissue cells (P<0.001)). The adhesion molecules showed unanimous rise in the blood and the tissue samples. In blood samples, CD11a: P<0.05 and CD11b: P<0.05 and tissue samples CD11a: P<0.01 and CD11b: P<0.01and CD54 in peripheral blood (P<0.05) and tissue (P<0.01) of AP was high as compared to controls. By simultaneous flowcytometric analysis, we determined the co-expression of a surface marker (CD4/CD8/CD14) and intracellular cytokine (TNF-alpha and IFN-gamma) in individual cells. The IFN-gamma producing CD8+T cells were elevated in pancreatic tissue (P<0.01). TNF-alpha producing cell numbers were significantly higher in tissue cells than in blood and also in CD8+ T cells (P<0.001). We conclude that monocyte function is affected in AP as shown by reduced HLA-DR numbers and lowered TNF-alpha producing cells. Moreover, the CD8+T cells appear to play an important role in cytokine synthesis at the effector site.     

CD14+CD16+ monocyte subpopulation in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring in early childhood. We have demonstrated that the activation of monocytes/macrophages plays a central role during acute KD. Recently, it has been reported that the CD14+CD16+ monocyte subpopulation plays a more important role in inflammation. In this study, we investigated the peripheral blood CD14+CD16+ monocyte subpopulation by flow cytometry, and serum levels of IL-10 and IL-12 using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation in patients with bacterial infections, mononucleosis and anaphylactoid purpura, since the cause of KD remains unknown. We observed an increase in the number of CD14+CD16+ monocytes with acute KD, which was a positive correlation with C-reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. In addition, we found that the serum levels of IL-10, but not IL-12, were higher during acute KD. These data suggest that increased peripheral blood CD14+CD16+ monocytes are part of the regulatory system of monocyte function during acute KD.     

Expression of the interleukin-2 receptor alpha (CD25) is selectively decreased on decidual CD4+ and CD8+ T lymphocytes in normal pregnancies

In a previous study, we demonstrated that the proportion of activated T cells (CD69+CD3+ and HLA-DR+CD3+) is higher in the endometrium and decidua after the luteal phase and throughout early pregnancy compared with in the peripheral blood. However, there was no difference in the proportion of CD25+CD3+ lymphocytes between the endometrium and peripheral blood. In this study, we further verify that the levels of CD25 on CD4+ and CD8+ T lymphocytes are not increased in normal pregnancy, although the levels of CD69 and HLA-DR are markedly increased. We also elucidate that the amounts of all three activation molecules on local T lymphocytes are down-regulated in pregnancy compared with that during the luteal phase. Nevertheless, these decreases are significantly lessened in anembryonic pregnancies with both normal and abnormal karyotyping. However, in peripheral blood, the down-regulation of activation molecules levels in pregnancy is only demonstrated on CD4+ cells and for HLA-DR on CD8+ cells. Furthermore, dual activation marker analysis demonstrated that the expression of CD25 appears to be dissociated from CD69 and HLA-DR on the same decidual lymphocytes. Because IL-2Ralpha plays a pivotal role in the development and propagation of functional T cells, its depressed expression may result in maternal tolerance of the fetal allograft.     

Expression of CD45R0 (UCHL1) by CD4+ and CD8+ T cells as a sign of in vivo activation in infectious mononucleosis.

CD45R0 (UCHL1), a member of leucocyte common antigen family, is expressed largely on previously activated or memory T cells. We examined CD45R0 expression of T cell subpopulations in patients with Epstein-Barr virus (EBV) induced infectious mononucleosis (IMN) as a sign of in vivo activation. Consistent with the notion that activated CD8+ T cells expand in acute IMN; the majority of CD8+ T cells in patients with acute IMN expressed CD45R0 to the similar extent to HLA-DR expression. Most CD4+ T cells in these patients also demonstrated marked expression of CD45R0 as well as HLA-DR antigens, compared with age-matched controls. Expression of CD45R0 by CD4+ T cells in patients with acute IMN was more notable than their HLA-DR expression. While predominant CD8+ T cells resulted in decreased percentages of CD4+ T cells, CD4+ T cells expressing CD45R0 were shown to be significantly elevated in absolute number. The results suggest that both CD4+ and CD8+ T cells may be activated by stimulation with EBV infection. The appearance of two T cell subpopulations expressing CD45R0 in acute IMN implies their immunoregulatory roles in the control of EBV-infected cells.     

Evaluation of serum levels of soluble CD4, CD8 and beta 2-microglobulin in visceral human leishmaniasis.

The levels of soluble CD4 (sCD4), sCD8 and beta 2-microglobulin (beta 2-M) were measured in sera from patients with visceral leishmaniasis during the course of infection. Levels of sCD4, sCD8 and beta 2-M were raised significantly above levels in normal sera and returned to the normal range after recovery. The decrease in the levels of sCD8 was related to a reduction of anaemia, leukopenia and thrombocytopenia. In contrast, sCD4 levels fluctuated during the period of infection. beta 2-M returned within normal range more rapidly than sCD8 secretion. Our results suggest that T cells are activated during infection, and that it is also possible that the raised levels of these soluble molecules play a role in the impairment of protective immunity.     

Infectious mononucleosis]

Infectious mononucleosis(IM) is a primary Epstein-Barr virus (EBV)infection. Since heterophil antibody negative IM is common in Japan, EBV antibody(presence of VCA-IgM or anti-EA, high titers of VCA-IgG in the absence of anti-EBNA) is useful for serologic diagnosis of IM. Although EBV causes the continuous growth of lymphoid cell lines in vitro and causes malignant diseases such as Burkitt lymphoma, nasopharyngeal cancer and malignant lymphomas in immunocompromised patients, IM is usually self-limiting, and after primary infection EBV persists in B cells throughout life without producing symptoms. In the present study, we studied CD8+ lymphocytes of patients with IM and demonstrate an increase in lymphocytes expressing HLA-DR and CD45RO, increase of intracellular pH, elevated plasma levels of sCD8, indicating activation of the subset. We also demonstrate activation of CD4+ T lymphocytes and gamma delta T lymphocytes. Activation of these immune systems in response to EBV is supposed to play an important role in assuring the benign course of IM.     

替比夫定对慢性乙型肝炎患者外周血CD4~+ CD25~+ CD127~(low) T和CD8~+ CD25~+ T细胞频率的影响及临床意义

目的探讨核苷类药物替比夫定对慢性乙肝患者(CHB)外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例的影响,并结合临床指标分析其临床意义。方法替比夫定抗病毒治疗22例CHB患者,在治疗前及治疗后3,6个月时,分别以流式细胞仪检测外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例,实时荧光定量RT-PCR检测Foxp3 mRNA的表达水平,荧光定量PCR检测血清HBV DNA水平,酶联免疫吸附法检测HBV标志物,全自动生化分析仪检测ALT水平。结果 CHB患者外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例显著高于对照组。替比夫定治疗3个月时,这两群细胞比例显著下降,Foxp3 mRNA的表达也显著下降;HBV DNA水平降至检测水平以下的CHB患者,其CD4+CD25+CD127lowT细胞也降至正常水平。治疗3、6个月时,HBeAg阴转率分别为9.1%和18.2%,发生HBeAg血清学转换者的CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例均降至正常水平。结论替比夫定能快速有效抑制CHB患者的病毒复制...     

Soluble CD8 in patients with rheumatic diseases.

An ELISA was used to measure soluble CD8 (sCD8) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD8 both in their sera and in their SF compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients, serial serum sCD8 levels initially fell and then rose preceding clinical improvement. In four patients where serum sCD8 levels rose and clinical improvement occurred, subsequent spontaneous decreases of serum sCD8 level preceded increased clinical disease activity by up to 2 weeks. In general, RA SF mononuclear cells (SFMNC) spontaneously produced high levels of sCD8. In contrast, autologous peripheral blood MNC only produced comparable levels after mitogenic stimulation. Incubation of SFMNC with increasing concentrations of human recombinant tumour necrosis factor alpha resulted in a dose-dependent potentiation of sCD8 release into the supernatant. There was an inverse relationship between the ability of SFMNC to release sCD8 and soluble interleukin-2 receptor, indicating that the CD8+ T cell population may play an important immunoregulatory role in RA.     

Immunopathology of skin lesions in Kawasaki disease]

Histopathological findings of skin lesions in Kawasaki disease (KD) have been characterized by extensive edema associated with the dilatation of small vessels in the papillary dermis. Although the inflammation in KD skin lesions was exudative in nature, neutrophil emigration was slight and most of the infiltrates were mononuclear cells. Immunofluorescent studies using skin biopsy specimens from 10 patients with KD aged from six months to eight years and seven months showed that the infiltrating cells in the dermis and epidermis were mainly composed of CD 3+ T cells and Leu M3+ macrophages, but not B cells. In double immunofluorescence staining with combinations of anti HLA-DR, CD4 and CD8 monoclonal antibodies, the infiltrating T cells were mainly CD4+ HLA-DR+ T cells. Leu 23% cell were also positive on these cells, thereby suggesting those to be activated. Studies of skin specimens obtained from the site of BCG vaccinations in patients with KD showed basically similar but more extensive lesions. As a control, the infiltrating cells in the dermis from patients with measles were examined. In contrast to KD, these cells were mainly CD8+ T cells. Together with the findings that the keratinocytes in the epidermis were positive for HLA-DR, the skin lesions in KD appear to be similar to those found in delayed type hypersensitivity. Thus, macrophages and helper T cells may play a crucial role in the pathogenesis of KD.     

Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease

We serially monitored cell surface antigen expression on mononuclear cells in peripheral blood isolated from patients with Kawasaki disease (KD), and found, for the first time, that a markedly increased number of CD4⁺CD8⁺ T lymphocytes was present in some of the patients (11 of the 24 cases). The cases of five of these 11 patients were complicated with coronary artery lesion (CAL); the 13 patients with normal numbers of CD4⁺CD8⁺ T lymphocytes did not have CAL. The patients' age, sex and grade of systemic inflammation evaluated by peripheral leucocyte count and serum C-reactive protein levels were not correlated to the number of CD4⁺CD8⁺ T lymphocytes. Other cell surface antigen characteristics of the CD4⁺CD8⁺ T lymphocytes included CD3⁺, CD45RA⁺, CD45RO⁺, CD16^?, and HLA-DR⁺. These results indicate that the surface antigen characteristics of the KD peripheral blood examined were the same as those of Epstein–Barr virus infection without CD45RA⁺. These findings provide useful information for the analysis of the pathogenesis of KD.     

T cell malignancy in Richter's syndrome presenting as hyper IgM. Induction and characterization of a novel CD3+, CD4-, CD8+ T cell subset from phytohemagglutinin-stimulated patient's CD3+, CD4+, CD8+ leukemic T cells

A patient is described, having Richter's syndrome and immunodeficiency with hyper IgM, who developed suppressor T cell lymphoma (CD3+, CD4-, CD8+) following untreated helper-suppressor T cell chronic lymphocytic leukemia (CD3+, CD4+, CD8+). The neoplastic T cells in both malignancies expressed interleukin (IL) 2 receptors but were deficient in typical CD2+ and CD5+ pan T antigens. Additionally, a large percentage of malignant lymph node T cells expressed HLA-DR+ activation antigens. In vitro immunoglobulin-production experiments demonstrated that the patient's leukemic blood T cells had an excess helper function for IgM synthesis but a suppressor function for IgG and IgA synthesis by normal B and T cells. The leukemic blood T cells demonstrated a poor response to phytohemagglutinin (PHA). A defect in IL 2 receptor expression was evident in PHA-stimulated leukemic blood T cells. Of interest was the observation that PHA stimulated the induction of a novel CD3+, CD4-, CD8+ T cell subset from patient's CD3+, CD4+, CD8+ leukemic blood T cells. These PHA-induced CD3+, CD4-, CD8+ T cell subsets produced an elevated proliferative response to PHA and concanavalin A, had a helper cell function for IgM synthesis and produced highly elevated amounts of IL 2.     

Characterization of CD4+ T helper cells in patients with Kawasaki disease (KD): preferential production of tumour necrosis factor-alpha (TNF-alpha) by V beta 2- or V beta 8- CD4+ T helper cells.

KD is an acute febrile illness in children characterized by coronary arteritis accompanied by aneurysm and thrombotic occlusion. The etiology of KD is unknown. It has been recently reported that KD is associated with the selective expansion of V beta 2+ and V beta 8.1+ T cells in peripheral blood lymphocytes (PBL), by studying the T cell receptor (TCR) repertoire of in vitro activated T cells. KD may therefore be caused by a superantigen [1-3]. To understand better the immunopathology of KD, we investigated TCR V beta 2 and V beta 8.1 expression on both the T cells of freshly isolated PBL and T cell clones (TCC) from patients with KD. Cytokine production by TCC was also studied. Blood samples were obtained from patients with acute (n = 20) and convalescent (n = 20) KD, age-matched children with non-infectious diseases (n = 18), and healthy adults (n = 20). Among these four groups, there were no significant differences in the percentages of either V beta 2+ or V beta 8.1+ T cells of freshly isolated PBL. The same was true for the CD4+ or CD8+ T cell subsets. One hundred and five TCC (98 CD3+ CD4+ CD8- and seven CD3+ CD4- CD8+) established from the affected skin, lymph node or PBL of six patients with KD were also negative for either V beta 2 or V beta 8.1 TCR. Sixty-eight of 105 TCC (65%) produced detectable levels (> 5 pg/ml) of TNF-alpha (6-1016 pg/ml), in the absence of any stimuli. In contrast, only 11 (10%) of 105 TCC or 7 (7%) of 97 TCC produced detectable levels of IL-2 or IL-6, respectively, in the absence of any stimuli. Stimulation with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) induced most TCC to produce higher amounts of TNF-alpha, IL-2 and IL-6. These results suggest that CD4+ T helper cells expressing TCR-beta other than V beta 2 or V beta 8 receptor, primarily through TNF-alpha production, are involved in the immunopathology of KD.     

Expression of CD8alpha identifies a distinct subset of effector memory CD4+ T lymphocytes

Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8alphaalpha homodimer, while the minor population was CD4lo CD8hi and expressed the CD8alphabeta heterodimer. The majority of CD4hi CD8alphalo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7- CD28- HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8alphalo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8alphalo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8alphalo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8alpha represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection.     

CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry

Many lymphocyte-activation-associated molecules are observed by immunohistochemistry in psoriasis vulgaris lesional skin. Non-T cells in lesional skin also express these molecules. We quantitatively measured the number of T cells expressing cell surface activation-associated molecules (CD69, CD25, CD122, HLA-DR) and co-stimulatory molecules (CD28, CTLA-4, CD80, CD86), including a Type 2 T cell marker (CD30) and CD11b, by flow cytometry of skin and peripheral blood. T cells in single cell suspensions of psoriatic lesional-epidermis-expressed HLA-DR (86%), CD69 (59%), CD25 (55%), CD122 (44%), and CD28 (91%). Dermal T cells showed similar percentages except for CD69 (17%). CD69 was found directly in lesional skin biopsies by immunohistochemistry. Both CD4 and CD8 subsets from lesional skin contained large populations of CD25+ cells with a bias towards CD8 activation in the epidermis and towards CD4 activation in the dermis. CD86, CD80, CTLA-4, CD30 and CD11b were expressed by less than 23% of the T cell populations from both the epidermis and dermis. CD30+CD4+ cells were found two-fold over CD8+ T cells. These results show that the majority of lesional lymphocytes are persistently activated. We also found the majority of Type 2 associated markers primarily on the CD4+ epidermal T cell population. Psoriatic blood contained elevated levels of T cells expressing CD25, primarily within the CD8+ subset. Thus the majority of lesional T cells expressed the three primary activation markers, while psoriatic blood T cells were distinguished by an increase in CD25, specifically within the CTL population.     

Pathophysiological functions of CD30+ CD4+ T cells in rheumatoid arthritis

High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis. We investigated the induction of CD30 and its functions in CD4+T cells from patients with established RA (disease duration >_2 years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC). Immunohistochemical analysis showed that only a small proportion of lymphocytes expressed CD30 in the ST (-1%). RA PB CD4+ T cells, after recovery from 6-day stimulation with anti-CD3 Ab and anti-CD28 Ab, showed in intracellular cytokine staining that CD30+ T cells could produce more interleukin-4 (IL-4) but less interferon-gamma. In the culture of RA PB CD4+ T Cells with anti-CD3 Ab and anti-CD28 Ab, blocking anti-CD30 Ab similarly inhibited the cell proliferation and activation of nuclear factor-kappaB on day 4 in RA and HC, but inhibited the apoptotic cell death on day 6 only in RA. These results indicate that despite high-level expression of sCD30, the anti-inflammatory activity of IL-4-producing CD30+ CD4+ T cells may be limited in the ST due to a poor induction of surface CD30 and a susceptibility to CD30-mediated cell death.     

Soluble CD8 and CD25 in serum of patients after heart transplantation.

To evaluate the diagnostic value of serum cytokine levels and cytokine receptor levels in the diagnosis of acute rejection after heart transplantation, we measured soluble CD8 and soluble CD25 in the serum of heart transplant recipients. The results were compared with endomyocardial biopsy (EMB) histopathology, lymphocyte activation by morphologic inspection of peripheral blood cells (cytoimmunologic monitoring), clinically manifested infections, and the maintenance immunosuppressive therapy. Significantly increased levels were observed in cases of lymphocyte activation in cytoimmunologic monitoring indicative of either rejection or infection. In clinically documented cytomegalovirus (CMV), bacterial, and Pneumocystis carinii infections, increased levels of soluble CD25 were observed. Soluble CD8 was only increased in a single case of P. carinii infection. A statistically significant correlation was calculated between the levels of soluble CD8 and whole blood cyclosporin A level. Considering chemotherapy, the levels of soluble CD8 showed an inverse correlation with the daily dosage of azathioprine. In conclusion, the levels of soluble CD8 and CD25 are associated with lymphocyte activation in peripheral blood, but do not differentiate between lymphocyte activation indicative of rejection or infection. No relationship was observed between levels of soluble CD8 and CD25, and EMB histopathology. Therefore, the assessment of these two cell products has no diagnostic potential for monitoring acute rejection after heart transplantation.