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M C Crevon

Publications and source records attributed to M C Crevon.

48 records · Page 3Linked to original sources

[Differential effect of azathioprine on the activation of B cells].

The in vitro antibody response to most T-independent antigens is inhibited by Azathioprine (Az) only at concentrations of 1-10 mug/ml. In contrast, B cell response to T-dependent antigens and to the T-independent antigen TNP-Polyacrylamide is sensitive to low Az concentrations (10(-2) mug/ml). These data suggest the existence of two different B cell activation processes : a. The activation by B cell mitogens or T-independent antigens with a mitogenic moiety which are Az-resistant; b. The activation by T-dependent antigens or T-independent antigens without a mitogenic moiety which are Az-sensitive.

Animals↗

Effect of azathioprine on in vitro antibody response. Differential effect on B cells involved in thymus-dependent and independent responses.

The effect of azathioprine (Az) on the primary in vitro antibody response of mouse spleen cell cultures has been studied. The response towards T cell-dependent antigens is suppressed by low Az concentrations (50% inhibition by 10(-2) mug/ml and 100% suppression by 10(-1) mug/ml). The same pattern is observed when Az addition is delayed until day 2, but the suppression is absent or partial when Az is added on day 3. In the early period (day 0 to day 1) the effect of Az is reversible upon addition of an excess of purine nucleosides. In contrast, the response to a T cell-independent antigen (TNP-T4) is relatively insensitive to Az, since 100-fold higher drug concentrations are required to obtain an inhibition. With the assumption that T helper cells are likely to be highly sensitive to Az, the effect of low Az concentrations on the other two cell populations involved in T cell-dependent responses has been evaluated. Adherent cells appear unaffected. In contrast, the B-cell response is markedly sensitive to Az, as shown by the effect of Az on the response of nude mouse cells to a T cell-dependent antigen in the presence of T-cell products, either specific or non-specific. On the other hand, the B-cell response to mitogens is resistant to az. Thus, Az has a differential effect on B-cell response according to the thymus dependency of the antigen. This may suggest the existence of two pathways for B-cell activation or two different B-cell subpopulations.

Animals↗

Cytokines in HIV infection.

Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.

Cytokines↗

IL-6 mRNA expression in CD25 positive malignant lymphomas.

We recently demonstrated that IL-2 is produced by reactive T cells in CD25-positive malignant lymphomas (ML). Using in situ hybridization, we investigated IL-6 mRNA expression in these CD25-positive ML. The ML tested included 9 anaplastic large cell lymphomas and 3 B-diffuse large cell lymphomas. Five CD25-negative ML were studied as controls. We show that IL-6 producing cells are present in all these ML. The density of positive cells was heterogeneous from case to case. However 3 cases of CD25-positive ML showed a dramatically higher density of IL-6 producing cells (70, 50, 43 producing cells per 10,000 cells, respectively) as compared to the other 9 cases of CD25-positive ML (mean 6.03 +/- 2.1 per 10,000). Morphological and topographical data suggested that several types of cells including fibroblasts, lymphocytes, macrophages and endothelial cells may synthesize IL-6. A combination of immunohistochemistry and in situ hybridization showed that reactive T cells and endothelial cells express the IL-6 gene whereas CD30-positive ML cells do not express this gene. Previous studies showed that IL-6 was capable to induce IL-2 receptor expression as well as production of IL-2 and stimulation of lymphomatous cells growth. Our present results indicate that the paracrine production of this cytokine may play a role in the proliferation of malignant lymphomas.

Adolescent↗

In vivo expression of IL-1 beta and IL-6 genes during viral infections in human.

Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.

AIDS-Related Complex↗

Interleukin-13 gene expression by malignant and EBV-transformed human B lymphocytes.

Expression of the IL-13 gene in malignant tissues from 26 human B-cell lymphoid malignancies was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). A positive signal was detected in 16 cases, which included high grade B lymphomas, follicular lymphomas and B-cell chronic lymphocytic leukemias. IL-13 mRNA was also detected in the 9 malignant B cell lines and in the 6 lymphoblastoid cell lines tested, as well as in freshly isolated malignant B cells from 2 patients with a Burkitt's lymphoma. Two of 8 T-cell lymphomas and 2 of 4 T-cell lines expressed the IL-13 gene. In contrast, IL-13 gene expression was not detected in any of the 5 non-lymphoid cell lines tested. No specific binding of radiolabeled IL-13 was detected on B cell lines, suggesting an absence of IL-13 receptors on such cells. This conclusion was also supported by the inability of IL-13 or anti-IL-13 antibodies to affect the growth of malignant B cells. Taken together, these results show that both malignant and EBV-transformed B lymphocytes, either freshly isolated or maintained as cell lines, express the IL-13 gene. This raises the question of the role of B lymphocyte-derived IL-13, a B lymphocyte stimulating cytokine, on the in vivo function of normal B lymphocytes as well as on the in vivo behaviour of B lymphoid malignancies.

Animals↗