Biomedical subjects

A M Nouri

Publications and source records attributed to A M Nouri.

At least 37 records · Page 2Linked to original sources

PubMed1995

Super-sensitive epithelial cell line and colorimetric assay to replace the conventional K562 target and chromium release assay for assessment of non-MHC-restricted cytotoxicity.

Using colorimetric MTT assay the susceptibility of a newly established bladder epithelial cell line, Fen cells was compared with conventional target cells, i.e., K562 and Daudi and other epithelial lines for investigation of non-specific killing activity (NK/LAK) of effector cells previously activated with interleukin-2 (IL-2). The results showed that Fen cell line was more sensitive than K562 and Daudi targets and this was seen whether the effector cells were IL-2-activated or not. The percent killing of effector cells from nine normal donors against Fen, K562 and Daudi targets at effector/target (E/T) ratio of 10/1 after IL-2 activation were 63.4 +/- 7.3, 42.6 +/- 4.3 (p = 0.0001) and 38.6 +/- 5.1 (p = 0.0001) respectively. The corresponding values for inactivated effector cells at 50/1, E/T ratio were 44.8 +/- 9.0, 25.1 +/- 8.3 (p = 0.0001) and 24.4 +/- 9.4 (p = 0.0001) indicating exquisite sensitivity of Fen cells to NK/LAK killing. The susceptibility of Fen cells was found to increase by pre-treatment of target cells with interferons (IFN). Thus the percent killing of untreated, IFN-alpha (1000 U/ml), beta (2000 U/ml) and gamma (100 U/ml) treated cells were 52%, 64% (p = 0.005), 70% (p = 0.001) and 67% (p = 0.001) respectively. These results indicated that Fen cells were more susceptible to NK/LAK killing than the conventional K562 and Daudi target cells. These results and the epithelial origin of Fen cells indicate that this cell line might prove to be a more realistic system to replace the conventional approach for assessment of NK/LAK activity in patients with cancer of epithelial origin.

Cell Death↗

PubMed1995

Epidermal growth factor-induced protection of tumour cell susceptibility to cytolysis.

Using radiobinding, transfection and colorimetric assays, the biological significance of epidermal growth factor (EGF) and its receptor on established human tumour cell lines was investigated. The intensity of class I major histocompatibility antigen (MHC) and EGF receptor (EGFR) expression on 20 tumour cell lines was investigated and showed no direct correlation (coefficient of correlation r = 0.43 and P = 0.06). furthermore, transfection of the beta 2-microglobulin gene into a class I negative bladder tumour cell line, resulting in the re-expression of fully assembled cell surface class I antigens, did not result in alteration of EGFR expression. However, there was an inverse correlation between the intensity of EGFR expression and the stimulatory response of cells to exogenously added EGF. The per cent inhibitions of cell proliferation by EGF at 100 ng/ml for A431 (highest EGFR expressor) and Scaber (lowest EGFR expressor) were 37 and -7%, respectively. The results also showed that cell lines isolated from testis tumours positive for epithelial markers (using pan keratin antibody LP34 as an epithelial marker), expressed significantly lower EGFR levels than cell lines from bladder tumours. The expression of EGFR receptor was not modulated by interferons (IFN-alpha and -gamma and only a minor effect with IFN-beta) or active supernatant containing a mixture of cytokines. Whilst the pretreatment of tumour cells with IFNs resulted in a significant increase in the susceptibility of tumour cells to interleukin-2-activated peripheral blood mononuclear cells, EGF treatment resulted in their protection. Thus, the per cent killing at an effector:target ratio of 20:1 for untreated cells and EGF (100 ng/ml), IFN-alpha (1000 U/ml), -beta (2000 U/ml) and -gamma (100 U/ml) were 53%, 33% (P = 0.004), 64% (P = 0.004), 69% (P = 0.001) and 66% (P = 0.001), respectively. These results indicate the complex interactions between EGF and EGFR and their relevance in modifying tumour cell behaviour. The hypothesis that the resistance to cytolysis of tumour cells induced by EGF stimulation may be a factor in the accelerated tumour growth seen in patients after traumatic tissue damage is discussed.

Cell Death↗

PubMed1994

Clinical and immunological effect of intravesical interleukin-2 on superficial bladder cancer.

Using immunocytochemical techniques the pattern of T cell markers and MHC antigens on peripheral blood mononuclear cells, and tumour biopsies of patients with superficial bladder cancer before and after intravesical human recombinant interleukin-2 (rhuIL-2) therapy (three cases at 1 MIU, four cases at 18 MIU and two cases at 54 MIU), was investigated. There was a slight but significant increase in the total number of circulating leucocytes, harvested from blood using density gradient technique, after intravesical rhuIL-2 treatment. Thus the mean +/- SD of seven cases before and after (more than 30 days of) IL-2 were 1.24 +/- 0.32 x 10(9)/l and 1.50 +/- 0.46 x 10(9)/l respectively (t-test, P = 0.032). However, this was substantially less than in samples collected after subcutaneously (six cases) and intravenously (seven cases) administering rhuIL-2, the results of which were 1.09 +/- 0.46 x 10(9)/l versus 2.22 +/- 0.68 x 10(9)/l (P = 0.016) and 0.84 x 10(9)/l versus 2.3 x 10(9)/l (P = 0.004) respectively. There was no demonstrable alteration in the percentage of cells positive for CD3, CD4, CD8, CD25 or CD56 in peripheral blood or urine populations in six patients treated with intravesical IL-2, or the pattern of MHC class I or II expression on tumour biopsies before and after treatment. Though this could have been a reflection of the fact that most of the cases had normal class I expression, there was one tumour with complete loss and one tumour with very low expression among the three cases showing stroma positivity for HLA-A3 antigens. Neither of these was altered by IL-2 treatment, nor was class II antigen expression, which was positive in five of nine cases before treatment. Given the lack of the expected major immunological changes and the poor clinical responses (one of nine complete responses lasted 3 months), it is concluded that the schedule has not produced an adequate dose intensity to induce lymphocyte activation and alternative schedules based on those developed from systemic treatment need exploration.

Administration, Intravesical↗

PubMed1994

Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium.

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer.

Adenocarcinoma↗

PubMed1994

The frequency of major histocompatibility complex antigen abnormalities in urological tumours and their correction by gene transfection or cytokine stimulation.

There is increasing evidence that loss of major histocompatibility complex (MHC) antigens from tumors may be a factor in escape from immune surveillance. In an attempt to quantify this phenomenon in bladder tumors, frozen sections were stained immunochemically and cell lines were tested in a radiobinding assay before and after treatment with interferon gamma (IFN gamma) and after attempts to correct the defect by normal human leukocyte antigen (HLA) gene transfection. Study of 68 tumor sections with W6/32 antibody against monomorphic class I demonstrated that 42% had reduced or absent staining compared with the intensity of stromal staining. Ten percent of cases had complete absence with W6/32, all of which were also negative for beta 2-microglobulin (beta 2-m) expression. Use of polymorphic antibodies for A2, A3, Bw4, and Bw6 increased this frequency of defects to 73%. Study of 21 tumor cell lines with W6/32 demonstrated negative staining in five (23%) that could not be induced by IFN gamma and reduced staining in three (14%) that could be increased by IFN gamma, the remainder showing normal levels unaffected by IFN gamma. An additional six (28%) failed to express class II in response to IFN gamma, leading to an overall incidence of abnormality of 65%. In no case did cotransfection of one cell line with a defect in one case transfection of beta 2-m gene into a class I negative line of fully assembled MHC class I antigens. It is concluded that the majority of tumor cells demonstrate some form of MHC class I and II defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

PubMed1993

Accurate and rapid assessment of MHC antigen upregulation following cytokine stimulation.

Three human tumour cell lines, A431 (cervical), Scaber (bladder) and Fen (bladder), were studied using immunohistochemical staining (IC), radiobinding (RB), immunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA) and dot-blot (DB) techniques in order to assess major histocompatibility antigen (MHC) induction in response to interferon-gamma (IFN-gamma). Induction of class II antigens by IFN-gamma was observed on all three cell lines using all techniques. Monoclonal antibody (Mab) staining showed that both Scaber and A431 lines were positive for intact class I (Mab W6/32), class I free heavy chain (Mab HC10) and beta 2 microglobulin (beta 2-m) (Mab BBM.1), while Fen cells were positive only with HC10. The IP technique demonstrated the presence of a 45 kDa band on precipitation of the Fen lysate with HC10 Mab, whereas no such band was observed when W6/32 was used. The DB technique confirmed the negative reaction with W6/32 and BBM.1 Mabs, while HC10 showed positive staining which was upregulated by IFN-gamma. Transfection of the Fen cells with the beta 2-m gene resulted in the surface expression of fully assembled class I molecules. The DB technique showed upregulation of class I antigens following IFN-gamma stimulation, while RB detected no significant increase in cell surface expression (t test; p = 0.104). The binding values for transfected Fen cells before and after IFN-gamma stimulation were 2000 +/- 48 and 2161 +/- 156 cpm respectively. These results demonstrate that the DB technique facilitates an accurate assessment of cytokine induced antigens, corrected against a background of total cellular protein synthesis. The ease of execution, simplicity, non-radioactive nature and economy make it the method of choice for routine screening prior to the selection of suitable patients for cytokine therapy.

Antigens, Neoplasm↗

PubMed1993

A new approach for measurement of cytotoxicity using colorimetric assay.

Using in vitro established tumour cell lines attempts were made to assess the suitability of tetrazolium salt reduction (MTT) assay to replace the conventional radioactive base techniques for measuring cell proliferation and cell killing. The optimum conditions for MTT loading time, concentration of MTT and the time for colour development were found to be 4 h, 5 mg/ml and 30 min respectively, conditions which were used for subsequent experiments. Analysis of the correlation between increasing cell numbers and optical densities (OD) showed a direct relationship with correlation of coefficient values of r > 0.98 and 10,000 cells/well was found to provide an accurate ODs for a wide variety of cell types. The accuracy of replicate readings of the assay was investigated by setting a wide range of cell numbers and the variation among seven replicates was calculated and found to be less that 6% of the mean values. The reproducibility of the assay for two cell lines was tested using the lines on four different occasions. The ODs for Jar and Fen cell lines were 0.80 +/- 0.01, 0.82 +/- 0.02, 0.90 +/- 0.02, 0.79 +/- 0.05 and 0.56 +/- 0.01, 0.58 +/- 0.03, 0.60 +/- 0.02 and 0.61 +/- 0.02 respectively giving maximum variation of less than 11% of mean on repeated testings. Comparison between the results of MTT with 3H-Tdr or 51Cr release assays showed a high degree of correlation over a wide range of cell numbers and cell types. The r values between the results of MTT with 3H-Tdr (for cell number ranging from 1.8 to 60 x 10(3)/well) or 51Cr release assays (for E/T ratios of between 5:1 and 40:1) were 0.89 (p = 0.001) and 0.96 (p < 0.03) respectively. These results demonstrate that it is possible to use the MTT assay interchangeably with radioactive base techniques to measure cell proliferation and cytotoxicity. The ease of its execution, safety and its suitability for analysing as few as 3000 cells makes this method a serious contender for replacing the conventional radioactive techniques.

Cell Division↗

PubMed1993

Generation of cytotoxic T lymphocytes from peripheral blood of leukaemic patients.

Peripheral blood mononuclear cells from 13 patients with acute leukaemia were used to establish long-term interleukin-2-dependent cytotoxic T lymphocytes. Cells were grown in RPMI medium containing interleukin-2 (IL-2, 100 U/ml) and 2.5% conditioned medium prepared by activating normal lymphocytes with phytohaemagglutinin. Proliferation of IL-2-dependent CD3-positive lymphocytes was seen in 1 of 2 acute lymphocytic leukaemia cases (ALL), 1 of 4 acute myelogenous leukaemia cases (AML) (M1) and 8 of 8 more differentiated AML. In 2 cases with detectable leukaemic cell markers (1 ALL and 1 AML) passageable cells were developed, that expressed normal T cell phenotypes (namely CD3, CD4 and CD8) at the expense of leukaemic cells. In 1 of 2 cases, long-term IL-2-cultured cells showed specific cytotoxic activity against autologous leukemic cells. The percentage killing against autologous and two allogeneic target cell lines at a 50/1 effector/target (E/T) ratio was 42%, 9% and 19% respectively. Similarly the cytotoxic activity of IL-2 activated from 4 different individuals against conventional tumour targets K562 and Daudi at a ratio of 50/1 was 29%-68% (median = 55%) and 34%-78% (median = 61%) respectively. It was also found that this killing potential of the activated cells was maintained for as long as culture was continued (median 23 days, range 17-75 days). The mechanism(s) of T cell proliferation at the expense of leukaemic blast cells in the case of a minority of leukaemic patients and the possible clinical therapeutic potential of these cells following in vitro IL-2 activation deserve further investigation.

Antigens, CD↗

PubMed1993

Immunological paradox in testicular tumours: the presence of a large number of activated T-cells despite the complete absence of MHC antigens.

Tissue sections from 22 seminoma (Se) and 10 teratoma (Te) patients were investigated for correlation between the presence of tumour infiltrating T-lymphocytes (TIL) and the expression of major histocompatibility complex (MHC) antigens using an immunoperoxidase staining technique. Complete absence of both class I and II antigens was observed in all Te and 20 out of 22 Se. The two positive Se showed only weak expression on 2% of tumour cells. Despite the absence of human leucocyte antigens (HLA) there were a large number of TIL scattered throughout the tissues in the case of Se with no predominance of CD4 or CD8 subpopulations in either group. T gamma positive cells were less than 5% of total CD3 positive cells in both Se and Te. The majority of the TIL were found to express activation markers, i.e. HLA class II antigens. Culture of tumour cell suspension with IL-2 produced passageable IL-2-dependent T cells from 10 out of 15 tumours. Studies with testis cell lines showed the complete absence of class I antigens in 2 out of 5 cases and the inability of interferon gamma (IFN gamma) to induce expression. IFN gamma also failed to induce class II antigens in three out of five of these lines. The immunological paradox of the presence of a large number of activated T-cells in testicular tumours despite the complete absence of MHC antigens remains unexplained and needs further investigation. Possible hypotheses are reviewed.

Histocompatibility Antigens Class I↗

PubMed1993

Intensity of class I antigen expression on human tumour cell lines and its relevance to the efficiency of non-MHC-restricted killing.

A modified tetrazolium reduction assay (MTT) was used to assess the relation between HLA class I antigen expression on tumour cells and their susceptibility as a target for non-MHC restricted LAK/NK cytotoxicity using interleukin-2 activated peripheral blood mononuclear cells (MNC) from normal individuals. At 20/1 effector/target ratio this ranged from no killing to 77%. The efficiency of killing was dependent on duration of effector cell culture with IL-2, peaking at day 10 and declining thereafter. This killing could be enhanced by addition of other cytokines including interferons alpha, beta and gamma. Study of a panel of 15 tumour cell lines using a single effector showed that there was no statistically significant inverse correlation (using Spearman rank test) between the degree of tumour class I expression and LAK/NK killing at 20/1 (r = 0.23 P = 0.39) and 10/1 (r = 0.30, P = 0.27) and at 5/1 E/T ratio r = 0.47, P = 0.08) respectively. Lack of inverse correlation between these two parameters came from study of one bladder tumour line (FEN), whose absent class I antigens had been corrected by transfection with beta 2 microglobulin gene. At high E/T ratio (20/1) there was an increase in the susceptibility of target cells to lysis (36% parent cell, 45% transfected cell), whilst at lower E/T ratios (1/1) there was significantly more killing of the non-transfected cells (10% vs 31%). The addition of anti-class I antibody W6/32 increased killing by 18% but this was non-specific as the same increase occurred with a class II antibody. These data suggest that overall there was not an inverse correlation between class I expression and LAK/NK killing at high E/T ratios, whilst at low (5/1 or lower) E/T ratios this correlation nearly reached statistical significance suggesting that the conflicting literature reports may be due to a threshold levels of effector cells above which the masking effects of MHC antigens disappears.

Antigens, Neoplasm↗

PubMed1993

Bladder and prostate cancer screening for human papillomavirus by polymerase chain reaction: conflicting results using different annealing temperatures.

Two sets of L1 ORF degenerative primers, GP5/6 and MYO9/11, have been used to screen for human papillomavirus (HPV) sequences in bladder tumours, cell lines and controls by polymerase chain reaction (PCR). None of the 14 bladder and prostate tumours or nine bladder cell lines contained HPV sequences when tested with L1 ORF primer pair GP5/6 at 40 degrees C annealing temperature. In contrast, use of the L1 ORF primer pair MY09/11 at this low annealing temperature consistently gave a 450 bp band, suggesting the presence of HPV. This occurred in all samples including the negative DNA controls. An increase in stringency to an annealing temperature of 55 degrees C resulted in an elimination of this band in the test and negative control samples. This finding may explain why there are contradictory reports in the literature, and further studies are in progress to clarify this issue.

Adult↗

PubMed1992

Induction of MHC antigens by tumour cell lines in response to interferons.

The induction of major histocompatibility complex antigens by interferons (IFN) on 17 established tumour cell lines was investigated by radio binding. One bladder (Fen) and two testis lines (Tera I and Ha) lacked class I antigens and IFN-gamma failed to induce their expression. However, IFN-gamma upregulated these antigens on lines expressing low class I antigens (Tera II and EP2102) with little or no significant effect on high class I expressing lines (T24 and RT112). In one bladder line (Wil) IFN-gamma, whilst failing to alter monomorphic class I, upregulated polymorphic HLA-A2 and A3 antigens. None of the 17 lines expressed class II antigens, but could all be induced by IFN-gamma except T24, TccSup, Tera II and Lan lines. This defect was not due to the absence of IFN-gamma receptor, since under the same conditions intracellular adhesion molecule 1 was upregulated. IFN-alpha, whilst failing to have any effect on class II, induced class I antigens. IFN-beta showed no activity on either class I or II antigens when used alone. However, in combination, it inhibited IFN-gamma induced class II antigens. Thus, it may be possible to study cells from fresh tumours to preselect the minority of patients who might benefit from cytokine therapy.

Antibodies, Monoclonal↗

PubMed1992

T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy.

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.

Animals↗

PubMed1991

Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: a new approach to study tumour immunology in vitro.

This paper reports the first example of tumour infiltrating lymphocytes (TILs) and a tumour cell line from the same individual and analyses their characteristics. The tumour cell line (CAT), derived from a patient with well-differentiated (G3pTa) TCC, has been in culture for 24 months and subcultured more than 100 times. Epithelial origin was established by electronmicroscopy and use of a range of monoclonal antibodies (Mabs) against cytokeratins. The TILs isolated from the same tumour expressed all the phenotypic characteristics of normal activated T cells and demonstrated low levels of cytotoxicity against the autologous tumour line (CAT). Comparison of cell surface molecules of these cells revealed the loss of HLA-B7, B44 and Bw6 from the CAT cells whilst maintaining HLA-A2, A3 and Bw4. Karyotypic analysis demonstrated three rearranged chromosomes (between chromosomes 4 and 11, 10 and 13, 11 and 17) on CAT cells. The potential that study of paired autologous tumour cells and TILs in culture offers for studying the role of MHC antigens in tumour rejection and the impact of different approaches to correcting the defect are reviewed.

Antibodies, Monoclonal↗

PubMed1991

Correlation between class I antigen expression and the ability to generate tumour infiltrating lymphocytes from bladder tumour biopsies.

Analysis of tissue sections from transurethrally resected bladder tumours using anti-CD3 antibody showed the presence of T lymphocytes in intra-epithelial layers in eight of 12 cases investigated. In a larger group of patients, Tumour Infiltrating Lymphocyte (TIL) growth was established from six of 19 cases using Interleukin-2 (IL-2) and conditioned medium (CM) and resulted in the expansion of TILs up to 100-fold. TILs from these individuals were phenotyped with W6/32 (anti-HLA-A,B,C), HB55 (anti-DR) and anti-CD3 antibodies using FAC sorter. The mean +/- s.d. frequency of positive staining with these antibodies were 96.7 +/- 4.0%, 87.5 +/- 10.0% and 82.5 +/- 7.8% respectively, indicating the activated nature of these T cells. The cytotoxic activity of these TILs against Daudi (ie, LAK activity) cell line at 25/1 E/T ratios varied from 26.3 +/- 3.2 to 62.8 +/- 5.2%. In one case where TILs and autologous tumour cell line were established, cytotoxicity studies showed low level of cytotoxicity against the autologous tumour cells (15.8 +/- 1.6%) compared with 62.8 +/- 5.2% against Daudi. Staining of tumour sections from these 19 individuals with W6/32 and BBM.1 revealed positive staining in six of six that developed TILs but only six of 13 (46%) cases, whose tumour failed to grow TILs (P less than 0.02, Fisher exact test). These results are indicative of the presence of IL-2 passageable T cells in bladder cancer biopsy and demonstrate that the successful expansion of these cells correlates with the normal expression of class I antigens on the tumour cells.

Antigens, CD↗

PubMed1990

Selective and non-selective loss of immunoregulatory molecules (HLA-A,B,C antigens and LFA-3) in transitional cell carcinoma.

The expression of the major histocompatibility complex (MHC) class I and II antigens and lymphocyte function-associated antigen-3 (LFA-3) was investigated using immunohistochemical staining of bladder tissue sections from 18 patients with transitional cell carcinoma (TCC) and two normal bladder specimens. The expressions of HLA-A,B,C antigens varied greatly between different tumours. Complete loss was observed in one of 18 cases. Moderate to strong expression of HLA-A,B,C antigens was observed in 10 of 18 cases with the remaining seven cases showing either weak expression or expression on only a proportion of the tumour cells. Selective loss of HLA-Bw6 was seen in one of 18 cases. In many cases heterogenous and often focal expression of HLA-D products was seen. In one case tumour cells not expressing HLA-DR antigens were adjacent to strongly HLA-DR expressing non-neoplastic bladder epithelium, indicating a lack of inducible HLA-DR in the tumour cells. LFA-3 was undetectable in two of 18 cases with the remaining 16 cases showing moderate to strong expression of the molecule. These findings indicate that a substantial proportion of bladder tumours have one or more of a wide range of different alterations in the expressions of immunoregulatory molecules that could contribute to escape from immune surveillance.

Adult↗

PubMed1987

Cytokines and the chronic inflammation of rheumatic disease. III. Deficient interleukin-2 production in rheumatoid arthritis is not due to suppressor mechanisms.

Despite the evidence for activated T cells in the joint in rheumatoid arthritis (RA), there is evidence of deficient lymphocyte proliferation to a variety of stimulants. We investigated the production of interleukin-2 (IL-2) after phytohemagglutinin (PHA) stimulation. We show that in the peripheral blood IL-2 production was similar in RA and controls (3.7 vs 3.0 U/ml, respectively). However, blood lymphocytes from patients with joint effusions produced significantly less IL-2 than from patients without effusions (1.8 vs 5.7 U/ml, respectively). The amount of IL-2 produced by synovial fluids (SF) cells was significantly less than that produced by the corresponding blood cells (1.0 vs 1.6 U/ml). Further experiments revealed that the decreased IL-2 production was not due to its removal by IL-2 receptor positive cells in the SF and cell mixing experiments did not reveal any suppressor influences.

Adult↗

PubMed1984

Human pregnancy serum inhibits interleukin-2 production.

Cell-mediated immunity may be depressed during pregnancy. We used the two way mixed lymphocyte reaction as an in vitro model of cell mediated immunity and studied the effect of pregnancy sera on this system by the amount of tritiated thymidine taken up by activated lymphocytes. We found that: (1) pregnancy sera contain a factor inhibiting the mixed lymphocyte reaction; (2) the inhibition of the mixed lymphocyte reaction induced by sera could be reversed by the addition of the supernatant from allogeneic mixed lymphocyte reaction; (3) pure interleukin-1 could not reverse the inhibitory effect and (4) recombinant interleukin-2 (IL-2) completely reversed the inhibitory effect of pregnancy sera on the mixed lymphocyte reaction. We conclude that a factor (or factors) present in serum from pregnant women is capable of inhibiting the generation of IL-2 during lymphocyte activation.

Blood↗