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N Odum

Publications and source records attributed to N Odum.

At least 91 records · Page 5Linked to original sources
PubMed1989

HLA-DP antigens and HTLV-1 antibody status among Japanese with multiple sclerosis: evidence for an increased frequency of HLA-DPw4.

Previously, an association between multiple sclerosis (MS) and HLA-DPw4 has been reported in Scandinavians. In the present study, the distribution of HLA-DP antigens was studied in 34 Japanese MS patients, all of whom fulfilled the criteria for definite MS. HLA-DP typings for DPw1 through w6 and the local specificity, CDP-HEI, were performed using the primed lymphocyte typing (PLT) technique. In addition, the patients were typed for a DR2+, Dw2+/Dw12- related, PLT defined specificity. The distribution of DPw1-w5 in 121 healthy, unrelated Japanese controls were from Nishimura et al., 1984; Nishimura, personal communication). Sera from all 34 patients and 38 controls (both from the HTLV-1 nonendemic, Kyoto region) were examined for the presence of HTLV-1 reacting antibodies by a highly sensitive radioimmuno assay (RIA) using two sources of HTLV-1 antigens, namely total crude protein preparations from disrupted HTLV-1 virions and affinity purified p24 HTLV-1 core proteins. The frequency of DPw4 was significantly increased to 35.3% in Japanese MS patients compared to 16.5% in controls (Relative Risk, RR = 2.8, p = 1.9 x 10(-2)). 41.6% of the MS patients gave clear typing responses with a PLT reagent which recognized a Dw2+ related specificity, which is higher than the frequency of Dw2 (6.8%) in Japanese. Fourteen of the 34 patient sera contrasting to none of the sera from 38 controls contained antibodies of IgG and/or IgM subclasses reacting with the HTLV-1 derived antigens. This difference is highly significant (P less than 1 x 10(-5)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor.

Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected. A thymic biopsy specimen showed severe abnormalities of both the thymic lymphoid and epithelial component with abortive medullary differentiation and almost an entire lack of Hassall's corpuscles. This patient represents a case of primary immune deficiency syndrome not previously described. Thymic deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide.

The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF beta (lymphotoxin). The intracellular levels of bioactive TNF alpha were minimal or undetectable in all cases. Cells from HLA-DR2+ individuals secreted significantly lower amounts of TNF alpha than cells from HLA-DR2- donors [2 ng/ml (1.5-4.4) and 7.5 ng/ml (3.9-8.3) respectively (medians 25-75%); P less than 0.01]. The difference disappeared if the cells were preactivated for 2 days with 1000 U/ml of recombinant gamma interferon (rIFN-gamma). In some individuals, the TNF alpha response increased considerably after IFN-gamma priming, in particular in those possessing the HLA-DR2 antigen. In contrast, there was no detectable difference in the production of IL-1 beta between the donors, and the IL-1 beta response decreased significantly after rIFN-gamma priming in HLA-DR2+ individuals [2.3 ng/ml (1.1-8.4) versus 7.2 ng/ml (5-7.9); P less than 0.05] and in HLA-DR2- individuals [3 ng/ml (1.1-5.3) versus 5.7 ng/ml (3.9-7.5); P less than 0.01]. There was no correlation between the TNF alpha and IL-1 responses and any of the other HLA-DR, -DP, or -B antigens. There was a significant positive correlation between the levels of TNF alpha measured by ELISA and by cytotoxicity assay. However, the TNF alpha-containing supernatants from 9 out of 37 individuals appeared to contain inhibitor(s) of the biological activity of TNF alpha. The presence of inhibitor(s) was not associated with any HLA antigens.

Adult↗
PubMed1988

Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules.

Recent investigations have demonstrated that the primary mixed lymphocyte reaction (MLR) is dependent on certain accessory molecules, e.g. CD4 and LFA-1. We have compared the requirements of the primary MLR and the responses of alloreactive, primed lymphocytes (PL) by inhibition studies using monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c-reactive MoAb significantly inhibited the primary MLR (inhibition = 25%, P less than or equal to 0.01; 48%, P less than or equal to 0.01 and 13%, P less than or equal to 0.05, respectively) but these MoAb did not inhibit the primed lymphocyte reaction (PLR). The CD11b-reactive MoAb had no significant influence on either of the responses. CD2- and CD4- reactive MoAb significantly inhibited both primary MLR (greater than 80%, P less than or equal to 0.01) and to a lesser extent the PLR (40-65%, P less than or equal to 0.01). A MoAb reactive with IL-1 beta inhibited the primary MLR (38%, P less than 0.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data indicated that PL seemed neither to bind exogenous IL-1 (as opposed to CD4+ PBMC) nor to possess membrane-bound IL-1. The differences between 'virgin' and primed, allogeneic T-cell responses indicate that profound changes in the functional capability of the responding T-cell population take place during the bulk expansion. The results indicate that during repeated priming with alloantigen and bulk expansion, the proliferative response of T lymphocytes becomes independent of (i) the interaction with the CD11 adhesion molecule(s), (ii) the CD5 molecule, and (iii) the cytokine IL-1 beta.

Antibodies, Monoclonal↗
PubMed1988

Interleukin 1-induced down-regulation of antibody binding to CD4 molecules on human lymphocytes.

Interleukin 1 (IL-1) is involved in the early activation of T lymphocytes. The CD4 antigen, described as a phenotypic marker of helper T cells, is also important in early T-cell activation by its ability to bind to MHC class II molecules on antigen-presenting cells, and to transmit positive (and negative) signals to the cells. We observed that purified human monocyte IL-1 as well as recombinant IL-1 alpha and IL-1 beta selectively decreased the binding of monoclonal antibodies to CD4 on the surface of otherwise unstimulated blood T cells, in contrast to prestimulated and continuously grown CD4+ cells. Under optimal growth conditions, the initial reduction in antibody binding to CD4 was followed by an apparent re-expression of the CD4 antigen even in the presence of high concentrations of IL-1. This re-expression did not occur if the cells were cultured at 4 degrees C, or after treatment with actinomycin D or cytochalasin B, indicating that protein synthesis and intact microfilament function were essential for re-expression of CD4 binding. The mechanism by which CD4 molecules are physically and/or functionally modulated by IL-1 is unclear.

Antibodies, Monoclonal↗
PubMed1988

Characterization and expression of the human T cell receptor-T3 complex by monoclonal antibody F101.01.

A murine monoclonal antibody (MoAb) F101.01 reacting with the T cell receptor (TCR)-T3 complex is presented. Immunohistological studies showed that F101.01 specifically stains T-zone lymphocytes in lymph nodes, tonsils, and splenic tissue. Two-colour immunofluorescence and flow cytometry demonstrated co-expression of the antigen defined by F101.01 and the pan-T cell antigens defined by CD2, CD3, CD5, and CD7 antibodies. Cells stained with CD4 and CD8 antibodies were both included in the F101.01-positive population, whereas CD16-positive natural killer cells (NK), B cells (CD19 and CD20), and myeloid cells (CD13 and CD33) were excluded. The target antigen of F101.01 co-modulated with the CD3-defined antigen (T3) and the TCR recognized by the MoAb WT-31. CD3 antibody and WT-31 both blocked binding of F101.01. F101.01 precipitated the TCR-T3 complex from lysates of 125I-labelled peripheral blood mononuclear cells (PBMC) and HPB-ALL, when the lysate was prepared with a detergent (digitonin) that conserves the TCR-T3 complex. FACS analysis of T cells from a patient with a T cell immunodeficiency demonstrated that delta-TCS-1-CD3+CD4+ and delta-TCS-1-CD3+CD8+ cells were brightly F101.01+, whereas a large subpopulation of delta-TCS-1+CD3+CD4-CD8- cells were weakly F101.01+. We conclude that F101.01 recognizes a conformational epitope of the TCR-T3 complex and that it reacts with the alpha beta TCR-T3 and the gamma delta TCR-T3 complexes with different intensities.

Antibodies, Monoclonal↗
PubMed1988

HLA-DP antigens are involved in the susceptibility to multiple sclerosis.

Forty-five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA-DP using Primed Lymphocyte Typing. Thirty-nine MS-patients and 63 controls were also DNA-typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA-DP and -DR genes. The frequencies of DPw4 were 93.3% in MS patients and 72.3% in controls (relative risk, RR = 5.4, p = 0.0014). The DR2 antigen was present in 75.5% of the patients and in 33.7% of the controls (RR = 6.1, p less than 10(-6)). DPw4 was not associated (i.e., was not in linkage disequilibrium) with DR2 in patients or controls. Thus, in MS the associations with DP and DR are independent of each other. However, the combined presence of DPw4 and DR2 gave a significantly higher risk than each antigen alone, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to MS.

HLA-D Antigens↗
PubMed1988

Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases.

This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due to cleavage of IL-2.

Binding, Competitive↗
PubMed1988

Humoral and cellular responses to Pneumocystis carinii, CMV, and herpes simplex in patients with AIDS and in controls.

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies.

To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk of a worsened clinical condition was 55 times higher in seropositive men whose responses to pokeweed mitogen were low than in other seropositive men. The corresponding relative risks for low transformation responses to cytomegalovirus and for a decreased absolute count of CD4 positive lymphocytes were 18 and six. The relative response to pokeweed mitogen is therefore a very sensitive short term predictive marker of the clinical condition of seropositive patients who have a CD4:CD8 ratio of less than 1.0.

AIDS-Related Complex↗
PubMed1987

Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes.

The restriction fragment length polymorphism (RFLP) of the class II HLA-DP subregion of the major histocompatibility complex (MHC) of humans has been unraveled by Southern blotting using DP alpha and DP beta probes in a study of 46 unrelated individuals with known HLA-DP types. Contrary to earlier preliminary findings with a limited number of enzymes, the RFLP appears to be quite extensive both with the DP beta (14 different DNA markers defined by individual fragments or clusters thereof) and the DP alpha (8 markers) probes, especially when enzymes recognizing only four base pairs were used. A few markers were absolutely or strongly associated with individual DP antigens, whereas most were associated with two or more DP antigens as defined by primed lymphocyte typing. Thus, Southern blotting seems feasible for typing for most DP determinants by specific fragments or subtraction between the various more broadly reactive DNA markers, and the RFLP provides further information on the DP subregion in addition to that provided by primed lymphocyte typing. In two recombinant families, the DP beta and DP alpha DNA markers segregated with DP antigens, whereas the DR beta, DQ beta, DQ alpha, and DX alpha markers followed the DR and DQ antigens.

Chromosome Mapping↗
PubMed1987

Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes.

The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors.

Adult↗
PubMed1987

Selective modulation of the CD4 molecular complex by Pseudomonas aeruginosa alkaline protease and elastase.

The binding of monoclonal antibodies against CD4 was specifically inhibited by treatment of human CD4+ cells with either alkaline protease (AP) or elastase (Ela), purified from Pseudomonas aeruginosa. Binding of antibodies against CD3 (pan T), CD5 (pan T), CD8 (T suppressor/cytotoxic), HLA-ABC, HLA-DR, HLA-DQ, HLA-DP/DR, and beta 2 microglobulin was not inhibited by AP or Ela. Heat-inactivation of the proteases at 65 degrees C for 20 min or treatment with the metal chelator EDTA abolished the inhibitory activity of both proteases. These findings may serve to develop novel immunological methods for the isolation and study of the lymphocyte CD4 structure, which plays an important part in the immune response.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells.

Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR) and antigenic stimulation by irradiated (7600 rad) post-BMT cells was observed in about two-thirds of the combinations tested (N = 20 and N = 9). The suppression of donor MLR and antigen responses ranged between 5-52% and 10-46%, respectively. Irradiated post-BMT cells significantly suppressed donor responses to suboptimal concentrations of phytohaemagglutinin (PHA) (median suppression: 28%; P less than 0.05; N = 7) and concanavalin A (Con A) (median suppression: 31%; P less than 0.05; N = 6). A clearly suppressive effect of post-BMT cells was observed when the ratios of CD4+/CD8+ post-BMT cells were lower than 0.5 (P less than 0.01). In three experiments, the depletion of the CD8- but not of the CD4-positive subset abrogated the suppression of the donor MLR by post-BMT cells. The suppression by post-BMT cells (irradiated) of MLR and mitogen responses was comparable whether the responding cells were derived from the donor or from HLA-DR-incompatible, unrelated individuals. The proliferative capacity of post-BMT cells compared to that of donor cells was assayed in the MLR with unrelated, HLA-DR-incompatible stimulator cells. A significantly decreased proliferative capacity (median 20% of that of donor cells) was found (P less than 0.01; N = 16). A weak inverse correlation (P less than 0.05; N = 16) between the proliferative and the suppressive capacity of post-BMT cells in the MLR was observed. These findings indicate that the decreased proliferative capacity upon mitogen, antigen, and alloantigen stimulation observed in most patients within 1-6 months after BMT may be partly due to non-specific suppression by CD8+ cells.

Adolescent↗
PubMed1987

A "new" supertypic HLA-DP related determinant detected by primed lymphocyte typing (PLT).

Primed Lymphocyte Typing (PLT) with local (CDP) and the 9th International Histocompatibility Workshop reagents (GNN) revealed "cross-reactions" between HLA-DPw6 and the GNN2B but not other DPw2 PLT-cells (GNN2A, CDP2A, CDP2B). We raised and bulk-expanded a well discriminating PLT-reagent (the JET-reagent) from an HLA-DR identical, DP, GNN2A, CDP2A, CDP2B compatible and GNN2B incompatible responder/stimulator combination. The JET-reagent defined a "new" determinant, JET, which was present in 11% of Danes. The JET determinant was associated with DPw2, w6, and DP-blank: 66% of DPw6 and DP-blank and 20% of DPw2-positive individuals were JET-positive. All JET-positive individuals belonged to this group, and six of these had two DP-antigens. JET segregated with DP-blank in three and with DPw6 in two informative families. In an HLA-DR/DPw6 recombinant family, JET segregated with DPw6 in the recombinant haplotype. The JET PLT-responses against all of six different JET-positive stimulators including the specific stimulator were strongly inhibited by the monoclonal antibody (MoAb) Tü39, which preferentially reacts with DP-molecules, but not by other HLA-specific MoAbs. The results indicate that JET is either a "new" supertypic DP-related specificity or a determinant, which shares epitopes with DP, of a "new" locus and in linkage disequilibrium with DP.

Antibodies, Monoclonal↗
PubMed1987

Increased frequency of HLA-DPw3 in severe aplastic anemia (AA).

Thirteen patients with severe aplastic anemia (AA) were HLA-DP typed using primed lymphocyte typing (PLT). The frequency of HLA-DPw3 was significantly increased to 69% in AA as compared to 22% in 160 controls (p less than 0.001; corrected p less than 0.01, RR = 8.0).

Adolescent↗