Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pertussis toxin (Ptx), an important adjuvant for inducing certain organ-specific autoimmune diseases in mice, exerts multiple effects upon the immune system. In addition to its adjuvant effects, which include enhancement of delayed-type hypersensitivity and increased antibody production. Ptx elicits a marked lymphocytosis with a concomitant decrease in thymic weight. In vitro studies indicate that Ptx acts directly on thymocytes and that both susceptible and resistant populations exist. It is believed that these susceptible cells are released into the circulation and account, in part, for the T cell component of the lymphocytosis. We have used flow cytometry to analyze the CD4, CD8, and Thy-1 phenotypes of thymic and peripheral T cells from Ptx-treated mice. In the thymus, there is a dramatic decrease in the number of CD4+CD8+ (double positive) cells at all doses tested (0.25, 0.50, and 1.0 microgram) by day 4 after Ptx treatment. The double negative and single positive populations remain relatively constant. Analysis of Thy-1 expression reveals a significant reduction in Thy-1hi thymocytes, with little change in the Thy-1lo population. Thus Ptx primarily affects and depletes, in a dose-dependent fashion, thymic T cells with an immature phenotype. These results mimic those of corticosteroids, although neither prior adrenalectomy nor treatment with the antiglucocorticoid RU486 are able to prevent the effects of Ptx. In the periphery of Ptx-treated animals, the relative increase in the number of CD4+ T cells is more than that of CD8+ T cells. Double positive and Thy-1hi cells cannot be detected in appreciable numbers. These results are consistent with the concept that Ptx may drive immature thymocytes through accelerated maturation for release into the periphery as single positive, predominantly CD4+, Thy-1lo cells. Increased numbers of such cells may in part account for the immunopotentiating effects of Ptx, particularly as they relate to the induction of organ-specific autoimmune disease. Treatment with purified Ptx beta-oligomer fails to elicit any of the responses described above, indicating that the holotoxin is required for such activities.
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PMID:Pertussis toxin-induced lymphocytosis is associated with alterations in thymocyte subpopulations. 134 51

A soluble fraction obtained from a testicular homogenate by precipitation with ammonium sulphate (ASPM) was emulsified with Freund's complete adjuvant (CFA) and injected into Wistar rats. At 50 days after the first immunization (total of three injections) the animals had developed moderate and multifocal testicular damage, characterized mainly by sloughing of the seminiferous epithelium. A delayed-type hypersensitivity response and circulating antibodies to ASPM were detected at different times with maximum levels at 50 days. The addition of Bordetella pertussis to the immunization did not increase the severity of the lesion but augmented the cellular and humoral immune response to ASPM. The phenotypic characterization of cells present in the lymph nodes draining from the site of immunization in animals injected with CFA alone (control group) revealed an increase in CD8+ T-cells and a low CD4/CD8 ratio. Conversely, rats immunized with CFA plus ASPM (experimental group) exhibited testicular damage and showed a significant decrease in CD8+ cells with a normal CD4/CD8 ratio. In conclusion, rats immunized with a testicular antigen developed focal aspermatogenic lesions and a concomitant specific immune response as well as lymph-node cell variations focused apparently on the CD8+ T-cell subpopulation.
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PMID:Testicular lesions and lymphocyte subpopulations in rats immunized with a soluble fraction of testicular homogenate. 176 27

We describe here a novel 26-kDa posphoprotein (p26), associated to the T cell receptor of CD4-CD8- lymph node cells of lpr/lpr mice, but not present in significant amounts in control mouse cells including polyclonally activated T cells. lpr p26 is constitutively phosphorylated on a tyrosyl residue. It is most likely a member of the G protein family and displays high GTP-binding and GTPase activities both unsensitive to interleukin 2. Bordetella pertussis toxin has no effect on the spontaneously enhanced GTP hydrolysis. The traits associated to p26 could contribute to the distinctive features of lpr/lpr double-negative cells.
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PMID:An abnormal signal transduction pathway in CD4-CD8- double-negative lymph node cells of MRL lpr/lpr mice. 183 87

Bordetella pertussis (Bp) infection in infants and young children can be associated with a significant increase in small lymphocytes with convoluted and cleaved nuclei (SLCCN) in the peripheral blood (PB). Buffy coat smears were studied that were prepared from the PB of 11 children with documented Bp infection, whose ages ranged from one month to four years. The white blood cell count ranged from 8.4 to 72.9 X 10(9)/L, with a mean of 28.6 X 10(9)/L. In all cases, the percentage of PB lymphocytes was in the normal range; the absolute lymphocyte count ranged from 6.5 to 54.8 X 10(9)/L, with a mean of 20.3 X 10(9)/L. SLCCN represented 12-56% of the lymphocyte population. B and T lymphocytes, identified with monoclonal antibodies with the use of an immunoalkaline phosphatase method, accounted for a mean of 21% and 53%, respectively, of the total nucleated cells (TNCs) on buffy coat smears. The T-helper and T-suppressor subsets represented 38% and 16% of the TNCs, respectively, resulting in a CD4-CD8 ratio of 2.4. Most SLCCN were of the T-helper phenotype; SLCCN of the T-suppressor subset and, rarely, of the B-cell type also were identified. These observations document that the lymphocytosis associated with Bp infection in infants and young children is characterized by the presence of morphologically abnormal cells that are predominantly CD4 positive and appear to represent an expansion of an immunophenotypically normal lymphocyte population.
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PMID:The morphologic and immunophenotypic assessment of the lymphocytosis accompanying Bordetella pertussis infection. 204 90

The B oligomer of pertussis toxin serves as a weak mitogen in the T lymphocyte, an effect which is associated with an early rise in cytosolic free calcium concentrations, as monitored by Fura-2 fluorescence. Upon co-administration of phorbol dibutyrate, a phorbol ester tumour promotor which activates protein kinase C, pertussis toxin-induced proliferation was synergistically enhanced, as measured by the increased uptake of [3H]thymidine, into cellular DNA. Although phorbol ester co-administration has often been associated with an inhibition of Ca2+-mobilizing pathways, phorbol dibutyrate pretreatment had no inhibitory effect on the pertussis toxin-induced calcium flux and may actually have enhanced this response slightly. Flow cytometric analysis of cell populations expanded by the combined regimen did not provide evidence for the preferential expansion of cells bearing either CD4 or CD8, the T-cell determinants representative of the helper-inducer and cytotoxic-suppressor subsets, respectively. Pertussis toxin and phorbol dibutyrate appear, therefore, to elicit polyclonal stimulation, rather than the selective activation of a given lymphocyte subset. Expression of the transferrin receptor, a marker for nutrient uptake, and CD25, the Tac component of the interleukin-2 (IL-2) receptor, was, however, synergistically enhanced in cells activated by the co-treatment procedure.
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PMID:Interactive effects of pertussis toxin and the phorbol ester tumour promotor, phorbol dibutyrate, on T-lymphocyte mitogenesis and the expression of phenotypic determinants. 246 42

Antibodies binding to a large subset of T-cell differentiation antigens, including CD2, CD4, CD5, CD6, CD7, CD8, Tp44, and CDw18, cause an increase in the cytoplasmic calcium concentration [( Ca2+]i) after the antigens are crosslinked on the cell surface. Similar crosslinking-induced signals were seen for a subset of mouse thymocyte differentiation antigens. The various antigens on human T cells differed in the extent of crosslinking required for generating the calcium signal, as evidenced by comparisons with monoclonal versus polyclonal second-step antibody. The [Ca2+]i increase that occurs after crosslinking represents mobilization of cytoplasmic calcium since the initial component of the signal is resistant to depletion of extracellular calcium by chelation with EGTA. The [Ca2+]i increase is completely inhibited by pretreatment of cells with pertussis toxin, indicating that a substrate for pertussis toxin regulates the signal transduction. Crosslinking of antigens other than the CD3/T-cell receptor complex did not result in T-cell proliferation. Crosslinking of CD2 and Tp44, but not other antigens, resulted in expression of functional interleukin 2 receptors. Comparisons of three different anti-CD3 antibodies showed that a second calcium signal was generated by crosslinking, even when the anti-CD3 antibodies were used at optimal concentrations.
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PMID:Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. 310 34

Previous studies have shown that the injection of estrogen into immature rats leads to an influx of leukocytes into the uterus. Using immunoperoxidase staining and monoclonal antibodies, we have characterized the nature of the infiltrating leukocytes in frozen sections of immature rat uteri obtained following the injection of estrogen, estrogen plus pertussigen, and the antiestrogen LY117018. Estradiol treatment for 2 days resulted in a significant increase in the number of uterine eosinophils, CD4 (W3/W25)-positive helper/inducer T lymphocytes, macrophages (MRC OX-42-positive cells), and Ia (MRC OX-6)-positive cells. In contrast, estradiol treatment failed to elicit a significant increase in the number of CD8 (MRC OX-8)-positive uterine cytotoxic/suppressor T lymphocytes and/or natural killer cells, as well as MAR 18.5- and/or MRC OX-12-positive B lymphocytes. The injection of LY117018 failed to elicit any changes in the number of cells expressing any of the phenotypes under investigation. The simultaneous injection of pertussigen, the major toxin responsible for the leukocytosis- and lymphocytosis-promoting activity of Bordetella pertussis, inhibited the estrogen-induced influx of eosinophils, macrophages (MRC OX-42-positive cells), and Ia (MRC OX-6)-positive cells but failed to prevent the influx of CD4 (W3/25) positive helper/inducer T lymphocytes. These results indicate that, in the immature rat, significant differences may exist in the susceptibility of various cell populations to the effects of estrogen, particularly with regard to uterine influx following estrogen stimulation. In addition, our observations suggest that either 1) the CD4-positive cells infiltrating the uterus following estrogen treatment may use a nonpertussigen-sensitive mechanism for chemotactic factor-receptor signal transduction or 2) a subpopulation of resident uterine cells can be induced to express the CD4 antigen following estrogen and/or estrogen plus pertussigen treatment.
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PMID:Immunohistochemical characterization of the estrogen-stimulated leukocyte influx in the immature rat uterus. 326 Jun 16

Experimental myasthenia gravis (EMG) was elicited in female AO rats, 8-12 weeks of age, by injection of 100 micrograms/rat Torpedo marmorata acetylcholine receptor (AChR)-protein incorporated in CFA. Bordetella pertussis, 24 x 10(9) microorganisms, rat, was injected simultaneously as additional adjuvant. Rats were sacrificed on the day of appearance of the clinical signs of EMG, and thymuses were used for histological analysis using stereologic method, and thymocyte subsets were estimated by flow cytometry. Two and three colour fluorescence was applied to determine DN (CD4-CD8-), DP (CD4+CD8+), SP-CD4+ (CD4+CD8-) and SP-CD8+ (CD4-CD8+) subsets, as well as thymocytes expressing TCR alpha/beta. Rats immunized with BSA and rats injected with saline were used as controls. From 56 rats immunized with AChR-protein, 44 rats developed the disease, between day 7 and 11 after immunization. Severity of disease varied from + to + + +. Stereologic analysis of tissue sections revealed a highly significant reduction of thymic cortex and hypertrophy of medulla in EMG thymuses. Similar, but very slight changes were observed in thymuses of rats immunized with BSA. Percentages of DN, SP-CD4+, and SP-CD8+ subpopulations were significantly increased, while the percentage of DP population showed a marked decrease. These preliminary data suggest an alteration of thymocyte maturational events. Whether these changes could be responsible for the initiation of autoimmunity, or are occurring as a secondary phenomenon, after EMG was already established following the injection of cross reactive antigen, is a matter for discussion.
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PMID:Thymus changes in experimentally induced myasthenia gravis. 790 60

Pertussis toxin (PT), from Bordetella pertussis, causes lymphocytosis and increased IL-4 and IgE secretion. The lymphocytosis is associated with impaired entry of lymphocytes into lymph nodes. The dose response of PT on IL-4 secretion was found to be similar to those for lymphocytosis and IgE production. These findings are consistent with the possibility that increased IL-4 production by PT may be related to its effect on lymphocyte circulation. The possibility that PT may selectively influence the entry into lymph nodes of subsets identified with CD45RB, CD4 or CD8 was tested by assessing the phenotype of lymph node cells. PT had no significant effect on the proportion of cells with these markers, either in unimmunized or in immunized mice. These findings indicate that PT does not selectively impair entry of these lymphocyte subsets into lymph nodes.
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PMID:Studies on the lymphocytosis induced by pertussis toxin. 808 66

Experimental autoimmune anterior uveitis (EAAU), a model of uveitis induced by sensitization to melanin associated antigen (MAA) derived from the iris and ciliary body, closely resembles human acute anterior uveitis. The immunopathogenesis of EAAU was studied by immunohistochemical detection of immune cells and the expression of Ia, ICAM-1 and LFA-1 antigens. Male Lewis rats were immunized with bovine MAA, mixed with CFA and pertussis toxin in the hind foot pad. Animals were examined daily by slit-lamp biomicroscopy and serially sacrificed up to 30 days. Immunohistology of the enucleated eyes was performed with monoclonal antibodies W3/25 (CD4), OX-8 (CD8), ED2 (macrophage), OX-33 (B cell), OX-6 (Ia), IA29 (ICAM-1) and WT.1 (LFA-1). During each stage of EAAU, CD4+ T cells predominated over both CD8+ T cells and macrophages in the uvea. Very few B cells were detected during each stage of EAAU. EAAU could not be induced by the adoptive transfer of sera obtained from immunized animals. Low levels of constitutive ICAM-1 and Ia were observed. An increase in ICAM-1 expression was first noted on the epithelial cells of the uveal tract and RPE on day 9 post immunization and preceded LFA-1 and Ia upregulation by approximately 2 days. The immunopathogenesis of EAAU appears to be linked to the presence of the CD4+ T cells.
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PMID:Immunohistochemical studies on melanin associated antigen (MAA) induced experimental autoimmune anterior uveitis (EAAU). 852 6


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