Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
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Alveolar macrophages (AMs) harvested from 32 HIV-infected patients with respiratory problems (opportunistic pulmonary infections, n = 12; other lung disease, n = 20) and 13 healthy controls were stained with a panel of 15 monoclonal antibodies directed against surface antigens implicated in cell function. Antigen expression was quantified by flow cytometry and expressed as relative linear median fluorescence intensity (RLMFI). On AMs of patients, as compared with controls, there was a significant enhancement of HLA DP (12.1 +/- 1.5 vs 6.5 +/- 0.9, p = 0.01, M +/- SEM, RLMFI units), CD11b (3.4 +/- 0.5 vs 1.7 +/- 0.4, p = 0.014), CD11c (8.9 +/- 1.0 vs 4.8 +/- 0.8, p = 0.0046), CD14 (2.1 +/- 0.3 vs 1.0 +/- 0.2, p = 0.0009), and CD33 (1.7 +/- 0.1 vs 1.0 +/- 0.2, p = 0.0093). No significant differences could be established for HLA-DR (36.9 +/- 5.8 vs 30.9 +/- 7.5, NS), HLA-DQ (3.4 +/- 0.3 vs 3.1 +/- 0.6, NS), CD54 (1.9 +/- 0.3 vs 1.2 +/- 0.1, NS), CD13 (2.5 +/- 0.6 vs 1.5 +/- 0.3, NS), CD36 (1.4 +/- 0.2 vs 0.9 +/- 0.3, NS), CD71 (10.3 +/- 1.9 vs 8.9 +/- 1.8, NS), CD25 (0.8 +/- 0.0 vs 0.9 +/- 0.1, NS), 27E10 (1.1 +/- 0.1 vs 0.8 +/- 0.3, NS), RM3/1 (1.9 +/- 0.4 vs 1.5 +/- 0.4, NS), and CD4 (1.5 +/- 0.3 vs 1.0 +/- 0.0, NS). The expression of CD14 and CD11b, but not of HLA class II antigens and CD71, was increased in the smaller cell population compared with the larger, thus suggesting monocyte recruitment. The increased expression of HLA-DP, CD11c, CD14, and CD33 on the patients' AMs was independent of smoking habits. The degree of immunodeficiency as indicated by the absolute peripheral CD4 count, the character of HIV-related pulmonary disease, and the prophylactic use of pentamidine or zidovudine did not significantly modify the antigen expression pattern. It is concluded that HIV infection may lead, most probably indirectly, to enhanced expression of surface antigens by local upregulation and/or recruitment of monocytes from the peripheral circulation. The functional significance of enhanced marker expression requires further clarification.
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PMID:Expression of surface markers on alveolar macrophages from symptomatic patients with HIV infection as detected by flow cytometry. 818 14

Tumor infiltrating lymphocytes (TIL) from malignant ascites or solid tumor specimens obtained from patients with ovarian carcinoma were expanded to large numbers in vitro (10(10)-10(11)) by a four-step method using AIM V medium and low concentrations of recombinant interleukin-2 (rIL-2). The expansion procedure employed 24-well culture plates, T-flasks, polyolefin gas-permeable bags (PGPB), and an artificial capillary culture system (ACCS). The mean number of mononuclear leukocytes introduced into the 24-well plates was 16.5 +/- 4.2 x 10(6) cells. TIL from a total of 16 patients were expanded only through the first three steps of the process (24-well-plates, T-flasks, and PGPB) with an overall expansion of 255 +/- 99 fold and mean duration of 27.4 +/- 2.2 days. TIL from 9 of 16 patients were expanded further through the fourth step (ACCS) of the expansion method. The cumulative fold-expansion in nine patients was 8044 +/- 4807 (mean +/- SEM), the median was 2876 and the mean expansion time was 47.1 +/- 4.7 days. TIL from seven additional patients did not grow in rIL-2. Six of these 7 patients received chemotherapy at least four weeks before the specimens were collected. Two ACCS were used in parallel to facilitate expansion of TIL. Viable rIL-2-expanded TIL in the range of 1 x 10(10)-1 x 10(11) were recovered from the two ACCS, a number sufficient for adoptive immunotherapy of patients with ovarian carcinoma. The rIL-2-expanded TIL were predominantly CD3+ CD4+ CD8- alpha beta TCR+, although CD3+ CD4- CD8+ alpha beta TCR+ T cell lines were obtained from certain patients. An increase (43 +/- 8 vs 75 +/- 13; P = 0.05) in the proportion of CD4+ cells was observed over the duration of the four expansion steps. However, CD8+ TIL-derived T cells lines were also expanded in the ACCS. The four-step expansion method described here has several significant advantages over existing techniques. It requires substantially less personnel, equipment and space and the risk of contamination during expansion of the cultures is decreased. These results demonstrate that the four-step method described here can be effectively used for the large-scale expansion of ovarian TIL for the treatment of patients with ovarian carcinoma by adoptive immunotherapy.
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PMID:Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunotherapy. 830 73

Sputum examination is a useful noninvasive method to study airway inflammation. We investigated the reproducibility and validity of the measurements of lymphocyte subsets in the sputum of 11 stable patients with asthma and 10 nonasthmatic smokers. Sputum was dispersed with 0.1% dithiothreitol. A differential cell count was made with Wright's stain. Aliquots were stained with antibodies to CD19 (B cells), CD3 (T cells), CD4 (helper), CD8 (suppressor), and the activation marker CD25 (IL2 receptor) on T-cell subsets and were assayed by flow cytometry. Sputum from patients with asthma compared with nonasthmatic subjects had more eosinophils (mean +/- SEM, 32.5 +/- 8.5 versus 1.3 +/- 0.5%, p < 0.01) and a higher proportion of lymphocytes that were B cells (16.2 +/- 3.2 versus 4.0 +/- 1.0%, p < 0.01), and these correlated closely with the eosinophils (r = 0.8, p < 0.01). Patients with asthma also had more activated T-helper cells (39.3 +/- 4.6 versus 9.0 +/- 9.0%, p = 0.05), but the comparison was limited to two smokers because of macrophage autofluorescence. The repeatability of measurements of helper T-cells (R = 0.94), suppressor T cells (R = 0.88), and activated helper T cells (R = 0.77) was good; repeatability of measurements of T and B cells could not be examined because these were reciprocals of each other. Asthmatic sputum has different lymphocyte profiles than sputum from nonasthmatic smoking control subjects. The results demonstrate a potential importance of antibody-producing lymphocytes in the airway and their relation to sputum eosinophilia in asthma.
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PMID:Elevated B cells in sputum of asthmatics. Close correlation with eosinophils. 856 94

One distinctive effect on T-cell development was analyzed by selectively increasing serum prolactin (PRL) concentration in thymus-grafted congenitally athymic nude mice and by neutralizing PRL in suspension cultures of thymus from 1-day-old neonatal mice. Flow cytometric analysis of single-positive CD4+ and CD8+ cells derived from inguinal lymph nodes revealed a CD4/CD8 cell ratio of 2.2 +/- 0.18 (mean +/- SEM) in thymus-grafted nude mice that is similar to the ratio for immune-competent BALB/c mice (2.0 +/- 0.06). Addition of the pituitary to thymus-grafted nude mice significantly elevated serum PRL (P < 0.005) and increased the CD4/CD8 cell ratio (2.8 +/- 0.12; P < 0.005), demonstrating preferential stimulation of CD4+ cell development. T cells in nude mice receiving sham (submandibular salivary gland) or pituitary grafts alone were below detectable levels. Suspension cultures of neonatal thymus treated with anti-mouse PRL antiserum resulted in 20% and 30% decreases in double-positive CD4+8+ thymocytes and thymocyte viability, respectively. A 10-fold increase in double-negative CD4-8- thymocytes expressing the interleukin 2 receptor alpha chain, CD25, was also observed concurrently. Our findings illustrate an important way in which PRL may participate in two interrelated mechanisms: the regulation of peripheral single-positive cells and the maintenance of thymocyte viability during the double-positive stage of intrathymic differentiation.
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PMID:Prolactin increases CD4/CD8 cell ratio in thymus-grafted congenitally athymic nude mice. 863 34

Lymphocytes are prominent components of human atherosclerotic lesions, but their presence in murine models of disease has not been confirmed. Lymphocyte subpopulations have been identified in apoE -/- and LDL receptor -/- mice fed a cholesterol-enriched diet for up to 3 months. ApoE -/- mice had higher serum cholesterol concentrations than did LDL receptor -/- mice during most of the feeding period, primarily due to large increases in VLDL concentrations. Total area of atherosclerotic lesions was greater at all times in apoE -/- than LDL receptor -/- mice (lesion area after 3 months on cholesterol-enriched diet: apoE -/-, 993 +/- 193 and LDL receptor -/-, 560 +/- 131 microns2 x 10(3), mean +/- SEM, n = 6 in each group). Lesions in apoE -/- mice contained larger macrophage-rich necrotic cores and more calcification than did those in LDL receptor -/- mice. Immunocytochemical analyses of tissue sections of ascending aortas performed with monoclonal antibodies to T and B lymphocytes and macrophages revealed that T lymphocytes immunoreactive for Thy 1.2, CD5, CD4, and CD8 were observed in lesions from both strains, but no B lymphocytes were detected. The density of Thy 1.2+ T lymphocytes in lesions was greatest at 1 month (apoE -/-, 98 +/- 23 and LDL receptor -/-, 201 +/- 40 lymphocytes/mm2, n = 6 in each group), decreasing in apoE -/- mice to 12 +/- 3 and in LDL receptor -/- mice to 51 +/- 20 lymphocytes/mm2 at 3 months. The presence of T lymphocytes in murine atherosclerotic lesions makes these animals potentially useful for studying the involvement of the immune system in atherogenesis.
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PMID:Lymphocyte populations in atherosclerotic lesions of apoE -/- and LDL receptor -/- mice. Decreasing density with disease progression. 869 40

Eosinophils and CD4+ lymphocytes are preferentially recruited into sites of allergic inflammation. A role for eosinophils in the recruitment of CD4+ lymphocytes has not been defined. We studied the capacity of human eosinophils to release chemoattractants for T lymphocytes. Supernatants of cultured eosinophils contained chemoattractant activity for lymphocytes, which was predominantly due to IL-16 (lymphocyte chemoattractant factor) and RANTES. With neutralizing Abs, eosinophil-derived lymphocyte chemotactic activity was diminished by a mean (+/- SEM) of 60 +/- 3% with polygonal anti-IL-16 Ab, 69 +/- 4% with anti-IL-16 mAb, 48 +/- 3% with anti-CD4 F(ab) (IL-16 receptor blockade), 40 +/- 4% with anti-RANTES mAb, and 88 +/- 5% with a combination of anti-IL-16 and anti-RANTES mAbs. IL-16 and RANTES were detectable in eosinophil-derived supernatants by ELISA. Eosinophils constitutively expressed mRNA transcripts for both IL-16 and RANTES detectable by reverse transcription-PCR and contained preformed IL-16 and RANTES demonstrable by ELISA of cell lysates and by immunocytochemistry of freshly isolated eosinophils. Thus, eosinophils are a source of two cytokines, IL-16 and RANTES, that are chemoattractants for lymphocytes as well as eosinophils. These data indicate that eosinophils could contribute cytokines to enhance the recruitment of additional populations of CD4+ lymphocytes and eosinophils.
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PMID:Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES. 878 20

T lymphocyte kinetics in liver allograft rejection were studied by measuring levels of activated (CD25+ and class II MHC+) T lymphocytes (CD5+) and T cell subsets (CD4 and CD8) in peripheral blood and the livers of allogeneic DA (RT1b) to LEW (RT1') and syngeneic LEW to LEW orthotopic rat liver transplants. Median survival was 10 days in untreated allogeneic rats (n = 17). Mean (+/- SEM) T lymphocyte class II MHC expression increased from 3.4 +/- 0.44% (day 2/3) to 4.9 +/- 1.1% (day 7) (p = 0.01). Complete sequential data were available for nine animals over the period of rejection confirming the increase in class II MHC expression (p = 0.05) and showing a decrease in CD25 expression (p = 0.05). There was a significant fall in CD4:CD8 ratio from day 2/3 to day 7 (p = 0.002). CD25 and class II MHC molecule expression and the CD4:CD8 ratio remained unchanged over the comparable period in the syngeneic LEW to LEW control model (n = 5, p > 0.3 for all comparisons). Cyclosporin A (5 mg/kg/day) was given orally for 17 days and then withdrawn to induce allograft tolerance in a further nine DA to LEW rats (median survival > 100 days). Samples taken at 2/3, 7, 17, 30, 40 and 100 days showed that T cell activation marker expression remained low during cyclosporin treatment (e.g. class II MHC expression 2.32 +/- 0.35%; CD25 expression 3.53 +/- 0.44% on day 7) but increased thereafter (e.g. class II MHC expression 8.19 +/- 0.65%. CD25 13.25 +/- 0.95% on day 100). There was a fall in CD4:CD8 ratio throughout (p < 0.001). Intrahepatic mononuclear cells were harvested from six normal livers, four allogeneic livers (at 10 days), five syngeneic livers (at 10 days) and five tolerant allografts (at 100 days). Rejecting grafts showed the highest proportion of T lymphocytes (66.8 +/- 4.0% vs 18.5 +/- 3.6% in controls, p = 0.01). T cell activation was higher in both rejecting and tolerant grafts versus normal control livers (p = 0.05 for CD25 and p < 0.01 for class II MHC expression). CD8+ lymphocytes predominated in the hepatic infiltrate in all models, although the majority of these cells were both CD5 and alpha beta T cell receptor negative. There was a higher proportion of T cells in tolerant allografts (44.5 +/- 5.2%, p < 0.01) compared with control animals. Serial changes in peripheral T lymphocyte subsets may be useful in monitoring experimental acute rejection. In peripheral blood, the increase in T cell activation and loss of CD4+ lymphocytes, along with evidence of increased intragraft infiltration by this subset implies that it has a primary role in the development of tolerance in this nodel.
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PMID:Peripheral blood and intrahepatic subsets of T lymphocyte activation and function in liver allograft rejection and drug-induced tolerance in rats. 884 89

Localized cutaneous leishmaniasis (LCL) in Colombia is caused primarily by Leishmania panamensis, a different species from those reported in Brazil, French Guiana, and Venezuela. Because different parasites may elicit disparate immune responses, the present study was undertaken to establish the leukocyte participation in the immune response against L. panamensis. Epidermal and dermal immune complexes were studied using an avidinbiotin immunoperoxidase technique and specific monoclonal antibodies. In LCL, the epidermis showed keratinocytes expressing intercellular adhesion molecule-1, a universal expression of human leukocyte antigen-DR, and a hyperplasia of CD1a+ Langerhans cells. The dermal granuloma observed had a mean +/- SEM value for the CD4/CD8 ratio of 0.80 +/- 0.06. The expression of the activation molecules CD25 (interleukin-2 receptor) and CD18 (lymphocyte function-associated antigen-1 beta), 10.5% and 38.1% respectively, suggests that many cells are primed and proliferating. Most T cells in the granuloma expressed alpha beta T cell receptor (TCR) (40.3%) whereas only a few (6.7%) expressed gamma delta TCR. The results show that Colombian LCL patients possessed the appropiate activation and accessory signals from immunocompetent cells to trigger the effector phase of the immune response and eventually eliminate the parasite.
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PMID:Immunocytochemical and histopathologic characterization of lesions from patients with localized cutaneous leishmaniasis caused by Leishmania panamensis. 891 90

The objective of the present study was to evaluate the prognostic utility in determining the risk of AIDS progression in HIV-1-infected asymptomatic hemophiliacs by in vitro immunoglobulin (Ig) synthesis. With this aim, a cohort of 28 HIV-1-seropositive hemophiliacs were studied. All showed the number of CD4 lymphocytes higher than 400 positive cells/mm3. In all cases the spontaneous and pokeweed mitogen-induced in vitro production of Ig by peripheral blood lymphocytes was evaluated at the beginning of the study and the ratio stimulated/spontaneous (Stim/Spon) synthesis was calculated. At the same time, the absolute CD8+ cell count, IgA serum immunoglobulin, p24 HIV-1 antigenemia, and beta2 microglobulin were calculated. These data were monitored during the 4-year follow-up of patients and compared with the stimulated/spontaneous Ig synthesis ratio to evaluate the predictive significance on the progression of HIV infection. According to the stimulated/spontaneous Ig synthesis ratio, hemophilic patients were separated into two categories. Group I included 12 subjects with a Stim/Spon ratio higher than 2 (the lowest value of normal controls) and group II included 16 cases with a ratio lower than 2. As control, in 36 HIV-1-negative hemophiliac individuals the stimulated/spontaneous Ig ratio ranged between 2 and 42; mean +/- SEM, 12.9 +/- 1.8. At the end of the 4-year follow-up, group I patients showed a CD4 count and clinical staging consistent with those of the first evaluation; in contrast group II demonstrated a significant decrease in CD4 lymphocytes and deterioration of clinical conditions. Our results show that a low Stim/Spon Ig ratio when the CD4 lymphocyte count was still normal appears to predict the depletion of this lymphoid subset and progression to AIDS before T CD8, IgA immunoglobulin, p24 HIV-1 antigenemia, and beta2 microglobulin abnormalities. In this setting, the stimulated/spontaneous Ig ratio may represent a useful tool for clinical decisions in HIV-1-infected hemophiliacs.
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PMID:Predictor of the rate of CD4 lymphocyte loss in HIV-1-seropositive asymptomatic hemophiliacs by in vitro immunoglobulin synthesis. 893 98

The mode of heterosexual transmission of human immunodeficiency virus (HIV) is not yet understood. The semen of HIV-infected men contains free virus and infected cells, and it is not known which of these is more important for sexual transmission of the virus to women. Some investigators have presented in vitro studies supporting a cellular mode of transmission of HIV and have suggested that infected lymphoid cells may act as the primary source of infection. This has become known as the "Trojan Horse" hypothesis. In vivo demonstrations of such events are lacking and are not likely to be forthcoming using human subjects. To investigate the ability of normal lymphoid cells to invade the cervicovaginal mucosa in an experimental animal, we stained C3H/He (H-2Kk) mouse peritoneal lymphoid cells with bisbenzimide, a vital fluorescent DNA-binding dye, and inoculated the cells atraumatically into the vaginas of progestin-treated, BALB/c (H-2Kd) recipient mice. Donor cells were identified in recipient tissues by their bisbenzimide-fluorescent nuclei and by fluorescein staining of the membrane antigen, H-2Kk. Donor lymphoid cells were observed in histological sections of recipient cervicovaginal mucosa and also in the iliac lymph nodes of 34 of 36 recipient mice 24 h after inoculation into the vagina. The number of donor cells in the iliac lymph nodes was 8.6 +/- 1.4 (mean +/- SEM) cells per mouse with a range of 0-35 cells per mouse. Approximately 28% of the donor lymphoid cells in recipient lymph nodes expressed CD4, which in humans is the receptor for HIV. We did not detect F4/80, a marker of mature mouse macrophages in the donor cell population, on any of the migrating cells in recipient lymph nodes. However, this negative result is equivocal, because the marker might be down-regulated after transfer or the migrating macrophages might be difficult to dissociate from the recipient lymph node tissue. These observations in mice support the suggestion that HIV-containing lymphoid cells in the semen of infected men may invade the cervicovaginal mucosa after sexual intercourse and deliver the virus to a woman's internal environment. However, both the donor cells and the recipient reproductive tract of the mice in the present study differed in significant respects from their counterparts in humans that might be involved in heterosexual HIV transmission. Further studies are needed to determine whether this possible mode of virus transmission is mainly responsible for heterosexual transmission of HIV in humans.
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PMID:Migration of foreign lymphocytes from the mouse vagina into the cervicovaginal mucosa and to the iliac lymph nodes. 911 58


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