DR-positive Cells Research Articles

Differences in Expression of Human Leukocyte Antigen Class II Subtypes and T Cell Subsets in Behçet's Disease with Arthritis.

It has been reported Human Leukocyte Antigen (HLA) gene polymorphism is a risk factor for the development of Behçet’s disease (BD). In this study, the association of HLA class II subtypes HLA-DP, DQ, DR, and T cell subsets in BD patients with arthritis was evaluated. Frequencies of HLA-DP, DQ, DR positive cells, and T cell subsets in peripheral blood leukocytes (PBL) were measured by flow cytometric analysis in BD, and compared to rheumatoid arthritis as disease controls and healthy controls. Frequencies of HLA-DQ were significantly decreased in whole PBL and granulocytes of BD active patients as compared to healthy controls. In monocytes populations, proportions of HLA-DR positive cells were significantly increased in BD active patients as compared to healthy controls. Proportions of CD4+CCR7+ and CD8+CCR7+ cells were significantly higher in BD active patients than in BD inactive in whole PBL. Frequencies of CD4+CD62L- and CD8+CD62L- cells in lymphocytes were significantly decreased in active BD than those in inactive BD. There were also correlations between disease activity markers and T cell subsets. Our results revealed HLA-DP, DQ, and DR expressing cell frequencies and several T cell subsets were significantly correlated with BD arthritis symptoms.

Monocytic HLA DR antigens in schizophrenic patients

A genetic association of specific human leukocyte antigens (HLA) DR genes and schizophrenia has recently been shown. These HLA play a fundamental role in the control of immune responses. Furthermore infectious agents have been proposed to be involved in the pathogenesis of schizophrenia. In this study we investigated the rate of HLA DR positive monocytes in schizophrenic patients compared to controls with a special focus on the adaption to in vitro stimulation with toll-like receptor ligands. Patients with schizophrenia and matched controls were included. For each individual, we evaluated the rate of HLA DR positive monocytes (either incubated at 37 °C or after stimulation with lipopolysaccharide or Poly I:C). We found a significantly higher percentage of schizophrenic patients with elevated HLA DR positive cells ( p = 0.045) as compared to controls. The adjustment rate from baseline levels of monocytic HLA DR positive cells to stimulation with Poly I:C was significantly lower in schizophrenic patients ( p = 0.038). The increased monocytic HLA DR in schizophrenic patients and the maladjustment of their monocytic HLA DR levels to an infectious stimulus might be a sign for a disturbed monocytic immune balance in schizophrenic individuals.

Induction and increase of HLA-DR antigen expression by immune interferon on ML-3 cell line enhances the anti-HLA-DR immunotoxin activity

In order to evaluate the impact of induction and increase target antigen expression on immunotoxin potency, we measured the potentiating effect of recombinant immune interferon-gamma (rIFN-gamma) on the cytotoxicity of an anti HLA-DR ricin A-chain immunotoxin (2G5 RTA-IT) on the myeloid cell line ML-3. After 48 h of incubation with rIFN-gamma (500 U/ml) the percentage of 2G5-positive cells increased from 40% to 79%, and the 2G5 mean density was enhanced by 10-fold (11,000 versus 110,000 molecules/cell). Concurrently, rIFN-gamma pretreatment induced a dramatic improvement of 2G5 RTA-IT dose-effect cytotoxicity, as well as immunotoxin cytotoxicity kinetics. When 2G5 RTA-IT was used at the optimal dose of 10(-8)M (the maximum dose which avoided non-specific ricin A-chain cytotoxicity), the immunotoxin-induced cell kill increased with the percentage of DR-positive ML-3 cells according to a similar linear-logarithmic function of rIFN-gamma concentration. Moreover, in the same range of rIFN-gamma concentrations, the killing values and the percentage of DR-positive ML-3 cells were similar if not identical. These findings imply that the enhancement of 2G5 RTA-IT cytotoxicity by rIFN-gamma is mainly related to the rIFN-gamma 2G5 antigen induction on HLA-DR negative cells when immunotoxin was used at 10(-8) M. Furthermore, 2G5 RTA-IT dose-effect cytotoxicity on DR-expressing ML-3 cells, when used at lower concentrations, was also increased by rIFN-gamma in a dose-dependent manner. This result suggests that for immunotoxin concentrations close to the limiting membrane saturation dose (10(-10)M), rIFN-gamma may not solely act by inducing HLA-DR expression on DR-negative ML-3 subpopulation but also by increasing individual cellular DR density on DR expressing ML-3 cells. Finally, our study showed that immunotoxin potency on malignant cell populations which display an heterogeneous antigen expression, could be greatly improved by the use of rIFN-gamma.

Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyophthy

Inflammatory and immunological mechanisms are implicated in the development of idiopathic dilated cardiomyopathy (DCM). Since activated T lymphocytes express surface HLA-DR antigens, an increased level of these cells in the circulation could indicated an ongoing immune response. While the role of activated T lymphocytes in experimental myocarditis has been elucidated, the contribution of T lymphocyte activation in clinical DCM remains unclear. We therefore examined the role of T-cell activation in peripheral blood samples obtained from 10 patients with DCM (mean age, 49 +/- 12 years) and from 10 age-matched healthy controls. Citrated whole blood was mixed with fluorescein isothiocyanate- or phycoerythrin-conjugated specific monoclonal antibodies and analyzed using a fluorescence-activated cell sorter (FACS). The ratio (%) of histocompatibility leukocyte antigen (HLA)-DR positive cells in the FACS gated lymphocyte population was significantly higher in DCM patients than in controls (7.9% +/- 5.3% vs 2.0% +/- 0.9%; P < 0.01). The expression of CD40L on T cells determined as mean fluorescence intensity (MFI) was also significantly higher in DCM patients than in controls (3.6 +/- 2.1 vs 1.8 +/- 0.4 MFI; P < 0.05). Furthermore, the ratios of T cells expressing HLA-DR and serum brain natriuretic peptide (BNP) levels closely correlated (P = 0.0008). We showed that HLA-DR on peripheral T cells significantly correlated with serum BNP levels and that high CD40L expression on T cells was concomitant with increased BNP levels (P < 0.05). Therefore the magnitude of T-cell expression, such as increased expression of HLA-DR and CD40L, contributes to myocardial dysfunction in DCM.

Circulating CD4+CD25+ and CD4+CD25+ T cells in myasthenia gravis and in relation to thymectomy.

Studies in experimental animal models of human autoimmune diseases have revealed that CD4(+)CD25(+) T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto-aggressive immunity. Myasthenia gravis (MG) is the best-characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4(+)CD25(+) versus CD4(+)CD25(-) cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4(+)CD25(+) cells. CD4(+)CD25(high) cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4(+)CD25(high) cells were similar in MG patients irrespective of treatment with thymectomy. CD4(+)CD25(+) cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4(+)CD25(-) cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)-DR-positive cells. In both MG patients and HCs, CD4(+)CD25(+) cells also contained a high proportion of CD95-expressing cells as possible evidence of apoptosis-proneness. Upon stimulation with anti-CD3/CD28 monoclonal antibodies, CD4(+)CD25(+) cells responded more vigorously than CD4(+)CD25(-) cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4(+)CD25(-) cells are mainly naïve T cells, in non-thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA-DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4(+)CD25(+) cells in MG, nor is the proportion of CD4(+)CD25(+) cells influenced by thymectomy.

Antigen-presenting cells at the liver tissue in patients with chronic viral liver diseases: CD83-positive mature dendritic cells at the vicinity of focal and confluent necrosis

Although defective functions of peripheral blood or splenic antigen-presenting cells (APCs) are implicated in the pathogenesis of persistent infection in murine and human hepatitis B virus (HBV) and hepatitis C virus (HCV)-carriers, little is known regarding liver-infiltrating APCs in patients with chronic liver diseases. Using immunohistochemical methodology and antigen retrieval technique, we have detected APCs such as HLA DR-positive cells, interdigitating cells (IDCs) and CD83-positive mature and activated dendritic cells (DCs) at the liver specimens from 39 patients with chronic hepatitis (CH) and 10 patients with liver cirrhosis (LC). All 3 types of APCs were detected at the portal areas in both CH and LC, the most abundant being the HLA DR-positive APCs. CD83-positive, mature and activated DCs were detected in patients with CH around the areas of focal and confluent necrosis at the liver parenchyma in close association with T cells. The localization of CD83-positive mature and activated DCs at the liver tissues from patients with CH warrants further study about the role of these DCs in the induction of hepatocellular damage. This may also help to design DC-based therapy for patients with chronic liver diseases.

Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load.

To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8(high) cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8(+) cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically defined memory and/or effector cells (CD45RA(-)CD27(+), CD45RA(+)CD27(-), and CD45RA(-)CD27(-)) were increased in HAM/TSP CD8(+) cells, compared with those of HTLV-I-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)-DR-positive cells was also increased in CD8(+) cells of HAM/TSP, compared with those in HLA-DR(+)CD8(+) cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Tax11-19-specific CD8(+) cells. The high frequency of memory and/or effector type HTLV-I Tax11-19-specific CD8(+) cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP.

Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation

Lymphopenia and immune deficiency are significant problems following allogeneic hematopoietic cell transplantation (HCT). It is largely assumed that delayed immune reconstruction is due to a profound decrease in thymus-dependent lymphopoiesis, especially in older patients, but apoptosis is also known to play a significant role in lymphocyte homeostasis. Peripheral T cells from patients who received HCT were studied for evidence of increased cell death. Spontaneous apoptosis was measured in CD3+ T cells following a 24-hour incubation using 7-amino-actinomycin D in conjunction with the dual staining of cell surface antigens. Apoptosis was significantly greater among CD3+ T cells taken from patients 19-23 days after transplantation (30.4% ± 12.5%,P &lt; .05), and 1 year after transplantation (9.7% ± 2.8%, P &lt; .05) compared with healthy controls (4.0% ± 1.5%). Increased apoptosis occurred preferentially in HLA (human leukocyte antigen)-DR positive cells and in both CD3+/CD4+ and CD3+/CD8+ T-cell subsets, while CD56+/CD3− natural killer cells were relatively resistant to apoptosis. The extent of CD4+T-cell apoptosis was greater in patients with grade II-IV acute graft-versus-host disease (GVHD) (33.9% ± 11.3%) compared with grade 0-I GVHD (14.6 ± 6.5%, P &lt; .05). T-cell apoptosis was also greater in patients who received transplantations from HLA-mismatched donors (39.5% ± 10.4%,P &lt; .05) or HLA-matched unrelated donors (32.1% ± 11.4%, P &lt; .05) compared with patients who received transplantations from HLA-identical siblings (19.6% ± 6.7%). The intensity of apoptosis among CD4+ T cells was significantly correlated with a lower CD4+ T-cell count. Together, these observations suggest that activation of T cells in vivo, presumably by alloantigens, predisposes the cells to spontaneous apoptosis, and this phenomenon is associated with lymphopenia. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT.

Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation

AbstractLymphopenia and immune deficiency are significant problems following allogeneic hematopoietic cell transplantation (HCT). It is largely assumed that delayed immune reconstruction is due to a profound decrease in thymus-dependent lymphopoiesis, especially in older patients, but apoptosis is also known to play a significant role in lymphocyte homeostasis. Peripheral T cells from patients who received HCT were studied for evidence of increased cell death. Spontaneous apoptosis was measured in CD3+ T cells following a 24-hour incubation using 7-amino-actinomycin D in conjunction with the dual staining of cell surface antigens. Apoptosis was significantly greater among CD3+ T cells taken from patients 19-23 days after transplantation (30.4% ± 12.5%,P < .05), and 1 year after transplantation (9.7% ± 2.8%, P < .05) compared with healthy controls (4.0% ± 1.5%). Increased apoptosis occurred preferentially in HLA (human leukocyte antigen)-DR positive cells and in both CD3+/CD4+ and CD3+/CD8+ T-cell subsets, while CD56+/CD3− natural killer cells were relatively resistant to apoptosis. The extent of CD4+T-cell apoptosis was greater in patients with grade II-IV acute graft-versus-host disease (GVHD) (33.9% ± 11.3%) compared with grade 0-I GVHD (14.6 ± 6.5%, P < .05). T-cell apoptosis was also greater in patients who received transplantations from HLA-mismatched donors (39.5% ± 10.4%,P < .05) or HLA-matched unrelated donors (32.1% ± 11.4%, P < .05) compared with patients who received transplantations from HLA-identical siblings (19.6% ± 6.7%). The intensity of apoptosis among CD4+ T cells was significantly correlated with a lower CD4+ T-cell count. Together, these observations suggest that activation of T cells in vivo, presumably by alloantigens, predisposes the cells to spontaneous apoptosis, and this phenomenon is associated with lymphopenia. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT.

Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause.

The purpose of this investigation was to localize and characterize white blood cell populations in the human ovary through its physiological life cycle. Ovaries from 30 women of reproductive age and from three post-menopausal women were embedded in paraffin or frozen. Clinical information and pathology review were used to obtain accurate menstrual cycle information and to ensure the absence of ovarian disease. Tissue sections were stained for leukocyte phenotypes and the numbers of white blood cells in the ovary were semiquantitatively assessed by two separate examiners using a 0-3 plus (+) scoring system. Our results demonstrated that macrophages and T lymphocytes were the primary immune cells of the ovary, the concentrations of which were dependent on the location and stage of development of the structures containing leukocytes. Developing follicles contained few (+) macrophages located in the theca, while atretic follicles possessed moderate (+2) numbers in the granulosa and few (+) to moderate (+2) numbers in the theca. Newly formed corpora lutea contained few (+) macrophages, while regressing corpora lutea contained abundant (+3) numbers. Human leukocyte antigen (HLA)-DR positive cells were located predominantly at sites where macrophages were present. T lymphocytes were generally not present in the developing follicle but focal, small (+) numbers were observed in blood vessels of the theca. Atretic follicles contained few (+) T lymphocytes in the granulosa and few (+) to moderate (+2) numbers in the theca. Few (+) T lymphocytes were present in new corpora lutea, while moderate (+2) to abundant (+3) numbers were present in regressing corpora lutea. T lymphocytes at all sites were UCHL1 positive. The CD4 (T helper) to CD8 (T suppressor) ration in the corpus luteum was 1:1. B-lymphocytes and natural killer cells were generally absent in the pre-menopausal ovary. The post-menopausal ovary, in contrast, only contained few (+) macrophages, T lymphocytes and natural killer cells in the stroma. In conclusion, our results indicate that the human ovary is an immunologically dynamic tissue containing activated macrophages and T lymphocytes which provide an anatomical basis for immunoendocrine interactions within the ovary.

Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation.

Prevention of graft-versus-host disease by depletion of CD6-positive T cells was studied in the dog. Donors were DLA-homozygous, recipients DLA-heterozygous with one DLA haplotype identical to the donor. Seven control dogs received untreated marrow and died of GvHD after full hemopoietic recovery within 28 days of transplantation. For prevention of GvHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells completely, but only part of CD8-positive cells and DR-positive cells. CD6-depleted marrow exhibited strong nonspecific "natural" suppression of the generation of cytotoxic T cells in vitro. Eleven dogs received CD6-depleted marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8 dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6-depleted marrow than after transplantation of untreated marrow. Four of these dogs were treated with G-CSF, and this accelerated the recovery of leukocytes, but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prevents GvHD across a DLA-haplotype difference, but rejection and mixed chimerism may occur. Treatment with G-CSF accelerates leukocyte recovery, but cannot prevent rejection.

Thymus cells in myasthenia gravis: a two-colour flow cytometric analysis of lymphocytes in the thymus and thymoma.

The thymus in patients with myasthenia gravis has germinal centres and the thymic lymphocytes spontaneously produce anti-acetylcholine receptor antibody in vitro. This suggests indirectly that the myasthenic thymus contains mature T and B cells that are autoreactive. We report a two colour flow cytometric analysis of the surface antigen phenotype of lymphocytes in the thymus and in thymoma in 24 patients and in 14 normal thymuses. The results show a decline in the proportion of double positive immature thymocytes with age. This process seems to be partially disrupted in patients with myasthenia gravis. In addition titres of anti-acetylcholine receptor antibody were positively correlated with the proportion of mature single positive T cells and non-T DR positive cells.

Congenital self-healing Langerhans cell histiocytosis with persistent cellular immunological abnormalities

We describe an infant who presented at birth with numerous haemorrhagic and encrusted skin lesions, hepatomegaly, lymphadenopathy, raised hepatic transaminases, leucopenia and thrombocytopenia. The diagnosis of Langerhans cell histiocytosis was confirmed by immunohistochemistry, which demonstrated the presence of CD1, S-100 and DR positive cells in the skin infiltrate. The skin lesions resolved spontaneously after 6 weeks but recurred at 3 months and again were self involuting with resolution by 9 months. Persistent circulating T-cell abnormalities, including T-cell lymphopenia and the presence and persistence of peripheral blood CD1 + cells were noted throughout the first year of life.

Histologic study of delayed reactions to coelenterates

We studied by immunohistochemistry three cases of delayed envenomation by coelenterates. The most prominent features were the grouping of human leukocyte antigen–DR–positive cells with Langerhans cells (S-100 positive) and helper/inducer T lymphocytes (Leu-1 +, Leu-3 +, and Leu-4 +). This indicates the possibility of a type IV immunoreaction in the delayed cutaneous lesions caused by coelenterates.

DR ANTIGEN EXPRESSION ON VASCULAR ENDOTHELIUM AND DUCT EPITHELIUM IN FRESH OR CULTURED HUMAN FETAL PANCREATA IN THE PRESENCE OF GAMMA-INTERFERON

The cells expressing MHC class II antigens play an important role in allograft rejection. We examined the expression of HLA DR antigens in human fetal pancreata ranging in gestational ages from 8 to 24 weeks. DR antigens were detected by immunohistochemical techniques using H4 and 40D MoAbs with immunoperoxidase staining and the ABC procedure. Vascular endothelium was identified by goat antibodies directed to human factor VIII-related antigens. DR expression on endothelium was further confirmed by double staining of tissue sections with H4 and anti-FVIII antibodies. In pancreata younger than 18 weeks of gestation, DR antigens were found on single cells that were randomly distributed throughout the pancreatic parenchyma. These cells resembled dendritic cells in morphology, as reported previously. Some vascular endothelial cells located in the intralobular connective tissues expressed DR antigens, but those in the pancreatic parenchyma were DR-negative. In 18-22 weeks, some endothelia of small vessels in the parenchyma became DR-positive. By 24 weeks, DR antigens were also expressed on medium-sized blood vessels, whereas intraislet capillaries and duct epithelia were DR-negative. The number of DR-positive cells increased rapidly from 11.2 cells/field (x400) in 12-14 week pancreata to 42.8 cells/field in 18-22 week pancreata. Most DR-positive cells in pancreata earlier than 18 weeks were dendritic-like cells, while those in older pancreata were endothelial cells. When pancreatic tissue fragments were cultured for two days in the presence of rIFN-gamma, vascular endothelium and duct epithelium, both of which were otherwise DR-negative, had become DR-positive. Even with this increase, DR-positive cell numbers were fewer in pancreata younger than 18 weeks of gestation as compared with those in older pancreata. We also detected clusters of epithelial-like cells that were clearly stained for DR antigens. These cells were located in the parenchyma where insulin positive cells were generally found. Their DR-antigens had not changed during the 3-day rIFN-gamma culture.

Calcitriol inhibits the PHA-induced production of IL-2 and IFN-γ and the proliferation of human peripheral blood leukocytes while enhancing the surface expression of HLA class II molecules

1 alpha-dihydroxivitamin D3 [calcitriol; 1,25-(OH)2D3], the most biologically active metabolite of vitamin D3, exerts several effects on peripheral blood mononuclear cells (PBMC). We report here the effects of calcitriol on PBMC proliferation and on the expression of some lymphocyte surface differentiation markers, as well as its action on lymphokine production. Calcitriol inhibited the proliferation of PHA-activated PBMC in a dose-dependent manner, with peak activity at 10(-8) M. Exposure of PHA-stimulated PBMC to 10(-8) M calcitriol for 3 days tended to increase the percent of CD4- and CD8-positive cells, though statistical significance was not reached. A more striking effect of calcitriol was seen on the expression of the non-polymorphic determinants of HLA class II DR molecules; in cultures stimulated with PHA for 3 or 4 days; 10(-8) calcitriol doubled the percent of DR-positive cells as compared to controls treated with PHA alone. This activity peaked at 10(-9) M, a supra-physiologic dose. After 3 days in culture, 10(-8) M calcitriol strongly inhibited the production of both IL-2 and IFN-gamma. This effect was evident at different PHA concentrations (0.5, 1.5 and 3.0 micrograms/ml), and almost disappeared at 10(-10) M. These results underline the immunoregulatory role of calcitriol, but well defined experimental models in vitro are needed for elucidating the relevance of this compound in physiology and, possibly, in therapeutics.

HLA-DR Display by Renal Tubular Epithelium and Phenotype of Infiltrate in Interstitial Nephritis

Renal tubular display of HLA-DR was estimated semi-quantitatively in 28 biopsies from 27 patients with various forms of tubulointerstitial nephritis (10 following use of non-steroidal anti-inflammatory drugs) using a monoclonal anti-MHC class II non-polymorphic antibody (DK-22). Normal donor kidneys and biopsies from patients with minimal-change nephrotic syndrome were examined as controls. The phenotype of infiltrating cells was also studied quantitatively, using monoclonal antibodies on frozen biopsy tissue; the number of cells infiltrating the interstitium was counted per tubular cross-section. Display of HLA-DR was seen in up to 5% of control tubular cells, but up to 100% expressed HLA-DR in tubulointerstitial nephritis biopsies. There was a correlation between the expression of HLA-DR and the severity of both tubular atrophy and tubulointerstitial fibrosis judged semi-quantitatively by optical microscopy. In controls up to 50 leucocytes per tubular cross-section were evident, but in patients with tubulointerstitial nephritis up to 1500 were observed, approximately 50% being T-lymphocytes, the majority expressing the helper phenotype except in early, active drug-induced tubulointerstitial nephritis; the remainder were mostly monocytes. There were no qualitative differences between the different causes of tubulointerstitial nephritis. Tubular DR expression correlated with the number of DR-positive cells in the interstitium, but not with total leucocytes or T-lymphocytes. HLA-DR tubular expression was greater in the early stages than late stages of NSAID-induced tubulointerstitial nephritis, but this relationship was not present in the group as whole. HLA-DR expression by renal tubular epithelial cells may play a role in localising or amplifying tubular injury in tubulointerstitial nephritis.

Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.

A hematopoietic cell (CFU-B1) capable of producing blast cell containing colonies in vitro was detected using a semisolid culture system. The CFU-B1 has the capacity for self-renewal and commitment to a number of hematopoietic lineages. Monoclonal antibody to the human progenitor cell antigen-1 (HPCA-1) and a monoclonal antibody against the major histocompatibility class II antigen (HLA-DR) were used with fluorescence activated cell sorting to phenotype the CFU-B1. The CFU-B1 was found to express My10 but not HLA-DR antigen; experiments using complement-dependent cytotoxicity to eliminate DR positive cells confirmed this finding. Pretreatment of marrow cells with two chemotherapeutic agents, 5-fluorouracil and 4-hydroperoxycyclophosphamide facilitated detection of CFU-B1 derived colonies, while diminishing or totally inhibiting colony formation by other hematopoietic progenitor cells. CFU-B1-derived colony formation was dependent upon the addition of exogenous hematopoietic growth factors. Media conditioned either by the human bladder carcinoma cell line 5637 or lectin stimulated leukocytes, as well as recombinant granulocyte-macrophage colony stimulating factor, interleukin 3 or interleukin 1 alpha promoted blast cell colony formation. By contrast, neither recombinant erythropoietin, recombinant interleukin 4, purified macrophage colony stimulating factor or recombinant granulocyte colony-stimulating factor alone promoted blast cell colony formation.

T-helper cell activation in bullous pemphigoid

In 10 untreated patients suffering from acute bullous pemphigoid the number of peripheral blood T cells (CD 3), T suppressor (CD 8) and T helper cells (CD 4) as well as activation antigens (DR and Tac) bearing lymphocytes was evaluated by monoclonal antibodies. While the pan-T cell population (CD 3) and T suppressor subpopulation (CD 8) were normal, the T helper subpopulation (CD 4) and the number of DR and Tac positive lymphocytes were significantly increased in the acute stage of bullous pemphigoid when compared to the age- and sex-matched controls. Phenotypically those DR positive cells belonged to the pan-T cell population (CD 3) at 66% and to the T helper subpopulation (CD 4) at 53% respectively. Under treatment with immunosuppressants the cell counts returned to normal suggesting a T helper cell activation to be involved in the acute stage of bullous pemphigoid.

Differential presentation of HLA-DR, DQ, and DP restriction elements by interferon-gamma-treated dermal fibroblasts.

Abstract IFN-gamma has been reported to induce expression of HLA class II (DR, DQ, DP) antigens on cultured human dermal fibroblasts (FB) by stimulating the de novo transcription of the alpha and beta chain genes of HLA-DR, -DQ, and -DP in these cells. We examined the relative nominal and alloantigen-presentation capacity of each HLA class II gene product on FB by using CD4-positive, TNP-specific T cell clones restricted by determinants on DR, DQ, or DP molecules, as well as allospecific, CD4-positive T cell clones recognizing DR-, DQ-, or DP-lymphocyte activating determinants. After IFN-gamma exposure, FB strains used for antigen presentation displayed a high percentage of DR-positive cells and a much smaller percentage of DP-positive cells, but no detectable DQ-positive cells by immunofluorescent techniques. FB stimulator cells supported proliferative responses of two DR-allospecific T cell clones and one TNP-specific, DR-restricted clone, but not another TNP-specific, DR-restricted clone. Despite only modest DP expression, FB stimulated both a TNP-specific, DP-restricted clone and a DP-allospecific T cell line. However, IFN-gamma treated FB failed to stimulate a TNP-specific, DQ-restricted clone and a DQ-allospecific clone. Our data indicate that IFN-gamma differentially regulates expression of functional class II lymphocyte activating determinants on FB antigen-presenting cells and that FB may fail to support DQ-directed T cell responses due to insufficient expression of DQ molecules on the FB cell surface. However, the quantity of DR or DP expressed on FB did not directly correlate with their ability to support T cell responses, indicating that additional factors, such as differences in T cell clone activation requirements, contribute to the capacity of FB to present class II allo- and antigen-restricting epitopes.