Biomedical subjects

F Shirakawa

Publications and source records attributed to F Shirakawa.

At least 19 recordsLinked to original sources

PubMed1989

Signal transduction pathway for IL-1. Involvement of a pertussis toxin-sensitive GTP-binding protein in the activation of adenylate cyclase.

Human Il-1 alpha induces the synthesis of kappa Ig L chains by the pre-B cell line 7OZ/3, IL-2R alpha by the human NK cell line YT, and PGE2 by human rheumatoid synovial cells. Pertussis toxin (PT) markedly inhibited all three IL-1-induced activation events. The inhibition by PT was associated with a decrease in IL-1-mediated cAMP production. PT also inhibited IL-1-stimulated cAMP production in crude membrane fractions from 7OZ/3, YT, and 3T3 fibroblasts. In addition, IL-1 stimulated GTPase activity present in the membranes IL-1-responsive cells. Furthermore, the IL-1-induced GTPase activity was sensitive to PT. PT induced the ADP-ribosylation of a 46-kDa substrate in membrane preparations from IL-1-responsive cells. Cholera toxin also induced the ADP-ribosylation of a 46-kDa substrate in the same membrane preparations. The present findings indicate that the IL-1R is linked to a PT-sensitive G protein that stimulates the activity of adenylate cyclase.

Adenosine Diphosphate Ribose↗

PubMed1989

Autocrine stimulation of interleukin 1 alpha in the growth of adult human T-cell leukemia cells.

In a previous study, we reported that adult T-cell leukemia (ATL) cells produce interleukin 1 (IL1)-like factors that stimulate murine thymocyte proliferation, the production of interleukin 2 (IL2), and the expression of IL2 receptors (IL2R) on normal human T-cells in the presence of concanavalin A. In this communication, we studied the effect of IL1 on the growth of ATL cells in vitro. When ATL cells freshly obtained from patients were cultured with recombinant (r) human IL1 alpha, IL1 beta, or IL1-like factors produced by ATL cell lines, the growth of ATL cells was stimulated in a concentration-dependent manner. Maximum stimulation was observed at a concentration of 50-100 units/ml of IL1. The expression of IL2R on ATL cells was also enhanced by IL1, but the production of IL2 was not induced. These effects of rIL1 alpha or beta were specifically inhibited by anti-IL1 alpha or anti-IL1 beta antibody. Furthermore, the spontaneous growth of ATL cells was also inhibited by anti-IL1 alpha antibody, but not by anti-IL1 beta antibody. ATL cells exhibited enhanced expression of IL1 receptors on their surface as detected by the binding of 125I-labeled rIL1 alpha. These results suggest that IL1 alpha produced by ATL cells stimulates the growth of ATL cells by an autocrine mechanism.

Humans↗

PubMed1989

Expression of IL-1 receptors on human peripheral B cells.

The expression of IL-1R on human peripheral B cells was analyzed by the binding assay with 125I-labeled human rIL-1 alpha and by the flow cytofluorometry by the use of FITC-conjugated IL-1 alpha. The proliferation and the differentiation of B cells stimulated with Staphylococcus aureus Cowan I (SAC) in the presence of T cell-derived factors were dependent on IL-1. By the binding experiment with 125I-labeled IL-1 alpha, B cells expressed only few IL-1R without any stimulations. When they were stimulated with SAC, IL-1R on B cells began to increase by only 1 h, reached the maximum level at 6 h. The binding of 125I-labeled IL-1 alpha to B cells was inhibited by the addition of either cold IL-1 alpha or IL-1 beta suggesting that IL-1R on B cells reactive for IL-1 alpha and IL-1 beta were identical. By Scatchard plot analysis, the existence of two classes of IL-1R on B cells was found. A major class of IL-1R (320 molecules/cell) has a lower affinity (Kd = 3.8 x 10(-10) M) and a minor class of IL-1R (70 molecules/cell) has a higher affinity (Kd = 4.4 x 10(-12) M). When B cells were stimulated with SAC, both lower and higher affinity IL-1R were increased to 1960 molecules/cell and 300 molecules/cell, respectively. Furthermore, IL-1R on B cells were also detected with FITC-conjugated IL-1 alpha by a flow cytofluorometer. Only 3 to 5% of B cells expressed IL-1R without any stimulations. When B cells were stimulated with SAC, IL-1R-positive B cells were increased to 20%. The addition of anti-class II antibodies inhibited B cell proliferation and differentiation induced with SAC, IL-1, and T cell-derived factors. Anti-class II antibodies also inhibited the number of IL-1R on B cells. These results suggest that the expression of IL-1R was induced as the initial stage of B cell activation and that class II Ag play an important role for the expression of IL-1R on B cells.

Antibodies, Monoclonal↗

PubMed1989

Circulating monocyte (macrophage)-specific antibodies in patients with autoimmune thyroid diseases.

We investigated the presence of circulating monocyte-specific antibodies (monocytotoxic activities) by a complement-dependent cytotoxicity test and the relations between these monocytotoxic activities and other immunological indices in patients with autoimmune thyroid diseases. Antibodies reactive for monocytes (macrophages) were found in the sera from patients with autoimmune thyroid diseases. These antibodies were present in both IgG and IgM fractions and specific for monocytes since they were absorbed by monocytes but not by lymphocytes or granulocytes; furthermore, lymphocytotoxic and granulocytotoxic activities were not changed after the absorption of the sample sera by monocytes. Also, these antibodies did not have cross-reactivity to thyroid-specific antigens demonstrated by absorption tests and their specificity was different from anti HLA-DR antibody demonstrated by a flow cytofluorometric analysis. Monocyte-specific antibodies are reactive for autologous monocytes as well as allogenic monocytes. Patients who had positive monocytotoxic activities had high levels of TSH receptor antibodies (TRAb) and antimicrosomal antibodies in Graves' disease, and monocytotoxic activities were significantly correlated with the levels of TRAb in Graves' disease. These results suggest that the monocyte-specific antibodies (monocytotoxic activities) were significantly correlated with the immunological activities in Graves' disease.

Adolescent↗

PubMed1989

Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein.

Interleukin 1 (IL-1) induces the synthesis of kappa immunoglobulin light chains and the expression of surface immunoglobulin in the murine pre-B-cell line 70Z/3 (J. G. Giri, P. W. Kincade, and S. B. Mizel, J. Immunol. 132:223-228, 1984). In the present study, we found that these effects of IL-1 are mimicked by cyclic AMP (cAMP) analogs and cAMP-elevating drugs. The induction of kappa immunoglobulin light-chain gene expression by IL-1 was associated with an increase in intracellular cAMP levels. Incubation of 70Z/3 cells with IL-1 or cAMP resulted in the activation of the kappa immunoglobulin enhancer, as detected by the induction of chloramphenicol acetyltransferase (CAT) in cells transfected with a kappa enhancer-CAT expression plasmid. In contrast, CAT plasmids lacking a kappa immunoglobulin enhancer were inactive in the presence of IL-1 or cAMP. Furthermore, IL-1 and cAMP analogs and inducers were found to induce the activation of a NF-kappa B-like DNA-binding protein that exhibited specificity for the kappa immunoglobulin enhancer. These results suggest that cAMP may play an important role as a second messenger for IL-1 in the induction of kappa immunoglobulin light-chain synthesis in pre-B cells via the activation of a DNA-binding protein that is similar or identical to NF-kappa B.

Animals↗

PubMed1989

In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C.

We have examined whether a precursor form of NF-kappa B, a DNA-binding protein that plays a role in the transcriptional control of several genes, including kappa immunoglobulin light chain and interleukin-2 receptor alpha subunit, could be activated in vitro by protein kinases. DNA-binding activity of NF-kappa B was induced in the cytosolic fraction of unstimulated 70Z/3 murine pre-B cells by incubation with the catalytic subunit of cyclic AMP-dependent protein kinase (PKA) or protein kinase C (PKC). In contrast, PKA and PKC did not activate NF-kappa B in nuclear extracts from unstimulated cells. Identical results were obtained with the human natural killer-like cell line YT, which can be induced to express the interleukin-2 receptor alpha subunit in response to interleukin-1, cyclic AMP, or phorbol 12-myristate 13-acetate. Furthermore, when nuclei from unstimulated cells were incubated with PKA- or PKC-treated cytosolic fraction for 30 min at 30 degrees C, NF-kappa B was translocated into the nuclei. This translocation did not occur at 4 degrees C and was inhibited by wheat germ agglutinin but not by concanavalin A. Our findings support the conclusion that NF-kappa B exists in the cytoplasm of unstimulated cells in an inactive form that can be converted by exposure to PKA or PKC to an active DNA-binding form that can translocate to the nucleus.

Amino Acid Sequence↗

PubMed1989

Establishment and characterization of a clonal human T-cell line, MKB-1 derived from a patient with acute myeloblastic leukemia.

A human T-cell line, designated as MKB-1, was established by cloning procedures in a suspension culture from a peripheral blood of a 17-year-old female patient with acute myeloblastic leukemia. The immunological marker profile of MKB-1 indicated that unlike a myeloid phenotype of the original leukemic cells, the cells were positive for CD3 (both cell surface and cytoplasm), T cell receptor (TcR) alpha/beta heterodimer, CD4, CD5, CD7, CD10, CD57 (Leu7), SN-1 and the cytoplasmic TcR beta chain. These findings indicate the T cell nature of the established cells. Terminal deoxynucleotidyl transferase (TdT) was also detected in 60%. We did not detect markers of human myeloid and B cell associated antigens, HLA-class II or immunoglobulin chains. Cytogenetic study revealed that the MKB-1 cells had a female hypo-tetraploid karyotype with chromosomal abnormalities including a translocation between chromosomes 10 and 14. The breakpoint of chromosome 14 of this translocation, 14q11.2, is known to be the location of TcR alpha and delta genes; t(10; 14) (q26; q11.2) is a variant type of a T cell neoplasm-associated translocation, t (10; 14) (q24; q11.2). The MKB-1 cell line is unusual in that its T cell characteristics are phenotypically and cytogenetically distinct from the original myeloid leukemia cells.

Adolescent↗

PubMed1988

Production of B cell-stimulating factors by B cells in patients with systemic lupus erythematosus.

The production of B cell-stimulating factors (BSF) by B cells in patients with systemic lupus erythematosus (SLE) was studied in vitro. B cells from SLE patients markedly proliferated and differentiated into Ig-producing cells by in vitro culture without any stimulation. The culture supernatant of these B cells contained BSF activity that stimulated Staphylococcus aureus Cowan I-treated normal B cells to proliferate and differentiate into Ig-producing cells. By a Percoll gradient density centrifugation, BSF-producing cells were enriched in the higher density fraction, but were reduced in the lower density fraction. The BSF also stimulated the proliferation and the differentiation of SLE B cells. By a Percoll gradient density centrifugation, SLE B cells responsive to the BSF were enriched in the higher density fraction, but were reduced in the lower density fraction. The Mr of the BSF was estimated as about 18,000 Da by Sephacryl S-200 column chromatography. The BSF fraction did not possess IL-2 and IFN activity, but possessed IL-1 activity, which stimulated murine thymocyte proliferative responses. The BSF activity was partially, but not completely, absorbed by an anti-IL-1 alpha antibody. Furthermore, the BSF possessed IL-4 activity, which induced not only the proliferative responses of normal B cells stimulated with B cell mitogens, but also the expression of low affinity Fc epsilon R/CD23 on normal B cells. The BSF also possessed IL-6 activity, which induced the proliferative responses of IL-6-dependent hybridoma cells, MH-60 BSF2. Moreover, human rIL-1, rIL-4, and rIL-6 stimulated SLE B cells. These results suggest that SLE B cells spontaneously produce the BSF such as IL-1 alpha, IL-4, and IL-6 and express their receptors on their surface, and the interaction between the BSF and their receptors stimulates SLE B cells to spontaneously proliferate and differentiate into Ig-producing cells as an autocrine mechanism.

Animals↗

PubMed1988

Production of bone-resorbing activity corresponding to interleukin-1 alpha by adult T-cell leukemia cells in humans.

The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1 alpha antiserum, but not with anti-IL-1 beta antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1 alpha and that this IL-1 alpha is one of the most important causes of hypercalcemia in ATL patients.

Biological Assay↗

PubMed1988

Inhibitory effect of anti-class II antibodies on human B-cell activation.

The role of class II antigens for B-cell activation was analyzed using purified human B cells and anti-class II monoclonal antibodies. The stimulation of purified B cells with Staphylococcus aureus Cowan I induced proliferation and differentiation into immunoglobulin-producing cells in the presence of interleukin-1 and T-cell-derived factors (B-cell growth factor and B-cell differentiation factor). The addition of anti-class II monoclonal antibodies inhibited B-cell responses. However, anti-class I monoclonal antibody did not inhibit B-cell responses. When mitomycin C and cycloheximide-treated B cells were added to the induction culture of B cells as the stimulator, B-cell responses were enhanced in a dose-dependent manner. Furthermore, the stimulator B cells also partially restored the suppressed B-cell responses which were induced by the pretreatment of B cells with anti-class II antibody. This enhancing effect of stimulator B cells on B-cell responses was inhibited by the pretreatment of stimulator B cells with anti-class II antibody. The treatment of B cells with anti-class II antibody and complement depleted the activity of both responder B cells and stimulator B cells. These results suggest that cellular interaction among B cells exists in the B-cell activation induced with Staphylococcus aureus, Cowan I and anti-class II antibody inhibits B-cell activation by interfering in this cellular interaction.

B-Lymphocytes↗

PubMed1988

Mechanism of spontaneous activation of B cells in patients with systemic lupus erythematosus. Analysis with anti-class II antibody.

The mechanism of spontaneous activation of B cells in patients with systemic lupus erythematosus (SLE) was analyzed by using anti-class II monoclonal antibodies in vitro. B cells from SLE patients showed enhanced proliferation and Ig production by in vitro culture without any stimulation. The number of Ig-producing cells increased during a 5-day culture period, but the addition of anti-class II antibodies such as anti-HLA-DR, DQ, or DP monoclonal antibodies inhibited these B cell responses in a dose-dependent manner. Anti-class I and anti-B1 antibody gave no effect. The inhibitory effect of anti-class II antibodies on B cell responses became more remarkable when B cells were cultured on a longer period. By a Percoll gradient density centrifugation, Ig-producing cells were enriched in the lower density fraction, but became depleted in the higher density fraction. However, B cells of the higher density fraction developed into Ig-producing cells after 5 days of culture and anti-class II antibodies inhibited this development. When mitomycin C- and cycloheximide-treated B cells were added to the in vitro culture of B cells as a stimulator, B cell responses were enhanced in a dose-dependent manner. T cells treated with mitomycin C and cycloheximide had no enhancing effect on B cell responses. Furthermore, the enhancing effect of the stimulator B cells was inhibited by the pretreatment of stimulator B cells with anti-class II antibodies. These results suggest that in patients with SLE the abnormality exists in B precursor cells which are easily activated by interacting with other B cells to differentiate into Ig-producing cells and anti-class II antibodies inhibit the B cell activation by interfering with this cellular interaction.

Antibodies, Monoclonal↗

PubMed1988

Cyclic AMP--an intracellular second messenger for interleukin 1.

We demonstrated that interleukin 1 (IL-1), a potent peptide mediator in immune and inflammatory responses, stimulates the synthesis of cAMP in a variety of IL-1-responsive cell targets. We also showed that cAMP analogs and cAMP-inducing agents can replace IL-1 in the induction of interleukin 2 receptors on lymphocytes as well as in phytohemagglutinin-induced murine thymocyte proliferation. By use of IL-1 and the cAMP-inducer, forskolin, a direct correlation between the induced level of cAMP and the degree of lymphocyte interleukin 2 receptor expression or thymocyte proliferation was established. Our results indicate that cAMP may be an important intracellular second messenger for IL-1.

Animals↗

PubMed1987

[Circulating HLA-DR (Ia) positive T cells and T cell activation by thyroglobulin, thyroid microsome and TSH-receptor in autoimmune thyroid diseases].

HLA-DR antigens are not expressed on normal circulating T lymphocytes, but recently it has become apparent that HLA-DR antigens are expressed on immunologically activated T lymphocytes, as well as monocytes, macrophages, and B lymphocytes. Namely, the HLA-DR antigens are considered to be one of the activated T cell antigens. It is apparent from the previous studies that increased numbers of HLA-DR positive T cells frequently appear in the circulation in systemic autoimmune diseases, such as RA and SLE. Furthermore, in such diseases, it is reported that the variations in circulating HLA-DR positive T cells are related to the activity of the diseases. In this communication, we examined the variations in HLA-DR positive T cells in the peripheral blood of the patients with autoimmune thyroid diseases. HLA-DR positive T cells were detected by cytotoxicity test using anti HLA-DR mouse monoclonal antibody (Leu-HLA-DR antibody) and rabbit complement. The results indicate that; 1) The percentage of HLA-DR positive T cells were increased in the patients with autoimmune thyroid diseases. 2) The changes of HLA-DR positive T cells accompanied with the stimulation by non-specific mitogens in vitro in autoimmune thyroid diseases did not differ from those in the normal controls. 3) The percentage of HLA-DR positive T cells increased by the stimulation of TSH-receptor and thyroid microsome in Graves' disease, on the other hand, it occurred by the stimulation of thyroglobulin and thyroid microsome in Hashimoto's thyroiditis. 4) The percentage of HLA-DR positive T cells were correlated with TRAb (TSH receptor Ab assayed by Smith's kit) in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

[Circulating monocyte (macrophage)-specific antibodies in patients with autoimmune thyroid diseases].

We investigated the presence of circulating monocyte-specific antibodies (monocytotoxic activities) by cytotoxicity tests and also the relationships between these monocytotoxic activities and the clinical data in autoimmune thyroid diseases. Subjects of this investigation include 16 patients with Graves' disease, 20 patients with Hashimoto's thyroiditis and 10 normal controls. To obtain monocyte-rich population, peripheral blood mononuclear cells of type 0 healthy donor were incubated on culture dishes for 12 hours and dish adherent cells were separated by pipetting. These monocyte-rich population were incubated with sample sera which were previously absorbed by lymphocytes of many different kinds of HLA types to eliminate anti-lymphocyte antibodies, and thereafter cytotoxicity tests were performed by adding rabbit complements. The monocytotoxic activities were expressed by %cytotoxicities and the value of %cytotoxicity over 3.9% (mean + 4SD of %cytotoxicities of normal controls) was considered to be positive in monocytotoxic activity. The results indicate that; 1) 8 patients (50%) of Graves' disease and 10 patients (50%) of Hashimoto's thyroiditis had positive values of monocytotoxic activity. 2) These positive values of monocytotoxic activity were markedly decreased after absorption of sample sera by monocytes, and these patients who had positive values of monocytotoxic activities to allogenic monocytes also had positive values of monocytotoxic activities to autologous monocytes. 3) Patients who had positive monocytotoxic activities also had high levels of TSH receptor antibody (TRAb) and anti-microsomal antibody, besides, monocytotoxic activity was significantly correlated with levels of TRAb in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1987

Expression of interleukin 1 receptors on human peripheral T cells.

The expression of interleukin 1 receptors (IL 1R) on human peripheral T cells was studied by the binding assay with 125I-labeled recombinant human interleukin 1 (IL 1) alpha and IL 1 beta and by the flow cytofluorometry with the fluorescein isothiocyanate (FITC)-conjugated IL 1 alpha. Peripheral blood lymphocytes expressed only few IL 1R without any stimulations. When they were stimulated with concanavalin A (Con A), IL 1R-positive cells began to increase by 4 hr, reached the maximum level at 48 hr, and then gradually decreased. The kinetics of the expression of IL 1 alpha R and IL 1 beta R showed the same pattern. Furthermore the binding of 125I-labeled IL 1 alpha to IL 1R on T cells was inhibited by the addition of either cold IL 1 alpha or IL beta, but not by interleukin 2 or interferons. The similar results were observed in the binding of 125I-labeled IL 1 beta. These results suggest that IL 1R on human peripheral T cells reactive for IL 1 alpha and IL 1 beta were identical. By Scatchard plot analysis, the numbers of IL 1R were estimated as 40 and 350 molecules per cell before and after Con A stimulation, respectively, and their Kd values were 3.1 X 10(-10) M and 2.8 X 10(-10) M. When purified T cells alone were stimulated with Con A, IL 1R were only marginally expressed. However, by the addition of monocytes, IL 1R were expressed on T cells in a dose-dependent manner. The maximum response was induced in the presence of 10% monocytes. The maximum IL 1R-positive T cells were approximately 30% by the detection of the flow cytofluorometry with FITC-conjugated IL 1 alpha. This enhancing activity of IL 1R expression on T cells by monocytes was inhibited by the addition of an anti-HLA-DR antibody or by the treatment of monocytes with the anti-HLA-DR antibody and complement. Furthermore T cell proliferative responses induced with IL 1 and Con A were also enhanced by the addition of HLA-DR-positive monocytes. These results suggest that IL 1R are expressed as the result of monocyte-T cell interaction in the early stage of T cell activation, and the expression of IL 1R on T cells and the responsiveness of T cells for IL 1 require the accessory function of HLA-DR-positive monocytes.

Antigen-Presenting Cells↗

PubMed1987

Production of interleukin 1 by adult T cell leukemia (ATL) cell lines.

The accessory function for T cell activation and the production of interleukin 1 (IL 1) of adult T cell leukemia (ATL) cell lines were studied in vitro. ATL cell lines such as Hut-102, MT-1, and MT-2 functioned as accessory cells for the stimulation of human T cell proliferative response induced with concanavalin A (Con A) and induced allogeneic mixed lymphocyte reaction. Cell lysates of three ATL cell lines and the culture supernatant of MT-2 cells had activities to stimulate murine thymocyte proliferative response. Then we studied physicochemical properties of the factors produced by MT-2 cells. The m.w. of the factors were approximately 15,000 by Sephacryl S-200 column chromatography, and their isoelectric point values were 5.4 and 4.8 by chromatofocussing technique. No fraction contained interleukin 2 (IL 2) activities to stimulate IL 2-dependent murine cytotoxic T cell line. The thymocyte-stimulating activities of the factors were absorbed with rabbit anti-IL 1 alpha antiserum, but not with anti-IL 1 beta antiserum. Furthermore, messenger RNA extracted from MT-2 cells hybridized to complementary DNA of IL 1 alpha, but not of IL 1 beta, by Northern blot hybridization analysis. The factors from MT-2 cells could stimulate the production of IL 2 and the expression of IL 2 receptors of human T cells in the presence of Con A as well as recombinant IL 1 alpha and IL 1 beta did, and these activities were also blocked by rabbit anti-IL 1 alpha antiserum, but not by anti-IL 1 beta antiserum. These results suggest that the factors produced by MT-2 cells correspond to IL 1 alpha. However, the accessory function of MT-2 cells for T cell activation was not blocked by rabbit anti-IL 1 antiserum. These results suggest that ATL cell lines produce IL 1-like factors, but the accessory function of ATL cell lines for T cell activation is mediated by some other mechanisms rather than by secreted IL 1-like factors.

Animals↗

PubMed1987

Monocyte (macrophage)-specific antibodies in patients with systemic lupus erythematosus (SLE).

Antibodies reactive for monocytes (macrophages) were found in the sera of patients with systemic lupus erythematosus (SLE). These antibodies were present in both IgG and IgM fractions and worked under both warm (37 degrees C) and cold (4 degrees C) conditions. These antibodies were specific for monocytes, because cytotoxic antibodies for monocytes were absorbed with monocytes, but not with T cells, B cells, and granulocytes. Furthermore, their specificity is also different from anti-HLA-DR antibody. The presence of these antibodies correlated with the activity of disease. They were found in 12 of 14 active SLE and 7 of 16 inactive SLE patients. The treatment of normal monocytes with these SLE sera and complement resulted in the depletion of their accessory function for T-cell activation and their phagocytic activity. In the previous paper, we reported that the accessory function of monocytes for T-cell activation was impaired in SLE patients. These results suggest that monocyte-specific antibodies play an important role in the pathogenesis of SLE through disturbing the monocyte regulatory function for immune responses.

Antibody Specificity↗

PubMed1987

Existence and immunological significance of circulating Ia+T cells in autoimmune thyroid diseases.

We investigated the percentage of circulating HLA-DR antigen positive (Ia antigen positive: Ia+) T cells and the additive proliferation by non-specific mitogens and thyroid-specific antigens by means of a cytotoxicity test in autoimmune thyroid diseases. Furthermore, we studied the stimulative function of circulating Ia+T cells in autologous mixed lymphocyte reactions. %Ia+T cells were significantly increased in patients with autoimmune thyroid diseases compared with those in normal controls. They were additionally increased by the stimulation of TSH-receptor or thyroid-microsome in patients with Graves' disease, and by the stimulation of thyroglobulin and thyroid-microsome in patients with Hashimoto's thyroiditis. As to the cellular immune function, circulating Ia+T cells stimulated Ia-T cells in autologous MLR in patients with autoimmune thyroid diseases. These data suggest that some of the T cells are already activated in vivo, that the activation of T cells may be by thyroid-specific antigens, and that these activated (Ia+) T cells may be able sequentially to induce the activation of inactivated (Ia-) T cells in autoimmune thyroid diseases.

Cytotoxicity Tests, Immunologic↗