Biomedical subjects

M C Crevon

Publications and source records attributed to M C Crevon.

At least 19 recordsLinked to original sources

PubMed2001

Expression of the chemokine RANTES in pulmonary Wegener's granulomatosis.

Wegener's granulomatosis (WG) is an inflammatory, destructive, angiotropic lesion. The inflammatory process involves accumulation of macrophages, lymphocytes, and polymorphonuclear neutrophils. We studied 6 lung biopsy specimens from patients with WG to characterize the cellular infiltrate and to analyze the mechanism of immune cell recruitment. We show that lymphocytes accumulating in WG lesions are mostly memory CD4(+)CD45RO(+) T lymphocytes and, although less numerous, CD8(+)CD45RO(+) T lymphocytes. Few if any B lymphocytes or natural killer cells are present within lesions. The chemokine RANTES (regulated upon activation in normal T cells, expressed and secreted) has been reported to recruit memory T lymphocytes and macrophages selectively. We used reverse-transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry to study its production in WG. RANTES was expressed at a higher level in WG lungs than in normal controls, especially around microabscesses. As visualized immunohistochemically in serial sections with anti-RANTES monoclonal antibody, RANTES production was produced mainly by macrophages. Expression of the gene coding for interferon-gamma (IFN-gamma), a potent RANTES inducer, was also studied. Its expression was also much stronger in WG than in controls. Our observations are consistent with a cascade of events leading to the recruitment of immune cells in WG, sequentially involving production of IFN-gamma by T lymphocytes and RANTES production by macrophages, leading to the homing of memory T-helper lymphocytes and macrophages. HUM PATHOL 32:320-326.

Adult↗

PubMed1998

Administration of interleukin 13 to simian immunodeficiency virus-infected macaques: induction of intestinal epithelial atrophy.

Increase Th2 cytokine production may contribute to some clinical manifestations of HIV infection, and studies have suggested that IL-13 rather than IL-4 is involved in these conditions. We directly tested this hypothesis by administrating IL-13 to SIV-infected macaques. SIV-infected rhesus macaques received a daily subcutaneous injection for 21 days of either IL-13 (10 microg/kg/day) or a placebo. The four macaques treated with IL-13 experienced body weight loss (9.95 +/- 0.71%) related to intestinal tract damage: they all suffered from a complete atrophy of duodenal villi. This was presumably due to premature epithelial cell death: proliferating Ki67+ cells in glandular crypts were as numerous as in control animals, but many epithelial cells developed apoptosis. The duodenal mucosa was infiltrated with cells expressing CD56 and PEN5, two markers of NK cells, and there was a deregulation of local cytokine and chemokine production characterized by a decrease in IL-10 gene expression (25% of controls) and an increase in gene expression for IFN-gamma (4-fold control), MIP-1alpha (8-fold control), and MIP-1beta (13-fold control). Thus, IL-13 can induce digestive epithelial cell injury in vivo in primates infected with a retrovirus. Therefore, its role should be considered in digestive manifestations of HIV infection as well as in other disorders associated with intestinal epithelial atrophy.

Animals↗

PubMed1997

Production and roles of IL-6, IL-10, and IL-13 in B-lymphocyte malignancies and in B-lymphocyte hyperactivity of HIV infection and autoimmunity.

We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a major factor of their proliferation. In other lymphomas, the IL-6 gene is expressed only in malignancies where differentiated malignant cells are present. In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells express the IL-6 receptor. In patients with HIV infection, the level of production of IL-6, IL-10, and IL-13 is not higher than those of other conditions with immune activation. However, IL-6 contributes to increased production of IgG and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node germinal centers, partly originating from follicular dendritic cells, which may explain some of the pathogenesis of this disease. In systemic lupus erythematosus, the critical cytokine is IL-10, which is produced in large amounts by B lymphocytes and monocytes and is responsible for autoantibody production. Taken together, these data emphasize the roles of IL-6 and IL-10, usually produced by nonlymphoid cells, on B lymphocytes, either malignant or hyperactivated.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Mechanisms of lysis by activated cytotoxic cells expressing perforin and granzyme-B genes and the protein TIA-1 in muscle biopsies of myositis.

OBJECTIVE: Polymyositis (PM) and cermatomyositis (DM) are inflammatory muscle diseases of autoimmune origin. A chronic mononuclear cell infiltrate is always present around PM and DM muscle damage. In PM, the predominant cells are activated cytotoxic cells, natural killer, and CD8+ T lymphocytes. Cytotoxic cells can kill the target cells via 2 mechanisms. Both pathways induce target cell death by releasing the molecules (granule exocytosis) perforin (PF), which attacks the target cell membrane and causes cell death by necrosis, and TIA-1 protein and granzyme-B (GZB), possibly responsible for apoptosis. We studied the mechanisms of lysis in muscle biopsies of myositis. METHODS: We used a panel of monoclonal antibodies to determine the phenotypes of reactive lymphocyte subsets, in situ hybridization to study the expression of PF and GZB genes, and immunohistochemistry to evaluate TIA-1 protein production in muscle biopsies from 14 patients with myositis (11 PM/3 DM). Results were compared to those obtained from muscle biopsies of 12 control patients with muscle weakness, including patients with muscle dystrophy and vasculitis, but without myositis. RESULTS: Abundant CD8+ cells, especially in endomysial sites in PM, formed the predominant phenotype. The predominant mononuclear cells observed in DM were CD4+ T cells and CD22+ B lymphocytes, in perivascular sites. The GZB and PF genes and the TIA-1 protein were expressed simultaneously in muscle samples from patients with myositis. GZB, PF, and TIA-1 positive cells were predominantly located in endomysial sites of PM, in the nonnecrotic muscle fibers. In DM, these positive cells were rare. CONCLUSION: In myositis, especially PM, cytotoxic cells may cause muscle damage and muscle cell necrosis and/or apoptosis by releasing several proteins (PF, GZB, and TIA-1 proteins) responsible for the lysis of these stimulating target cells. Some drugs (prednisone and cyclosporine) inhibit the release of GZB and PF. Their efficacy may be due in part to this inhibitory effect.

Adult↗

PubMed1995

Intratumoral activation of CD8-positive cytotoxic lymphocytes in acquired immunodeficiency syndrome lymphomas.

The incidence of lymphomas is unusually high in human immunodeficiency virus (HIV)-infected patients. Because cytotoxic T lymphocytes (CTL) represent a major mechanism of the antitumoral immune response in immunocompetent individuals, we asked whether intratumoral activation of CTL was impaired in acquired immune deficiency syndrome (AIDS) lymphomas. Immunohistochemical experiments showed that in AIDS lymphomas intratumoral CD8-positive T lymphocytes accumulated and expressed the TIA-1 antigen, a marker of cytotoxic cells. Flow cytometry studies and in situ hybridization of lymphomatous tissue confirmed the differentiation of CD8-positive cells in cytotoxic cells and their activation, as assessed by their expression of CD38 and human leukocyte antigen (HLA) DR markers as well as the perforin and granzyme B genes, which code for two molecules involved in target cell killing. On average, perforin-producing cells were as numerous in AIDS lymphomas (5,647 +/- 2,655 cells/cm2) as in lymphomas from immunocompetent individuals (3,294 +/- 1,544 cells/cm2). The density of activated CD8-positive cells in the 22 AIDS lymphomas tested was not correlated with peripheral CD4-positive cell counts. These results suggest that in AIDS lymphomas the steps of differentiation and activation of cytotoxic CD8-positive cells are not altered by immune deficiency and that they can take place through pathways relatively independent of CD4-positive T lymphocytes. Thus, other mechanisms of immune deficiency should account for the increased frequency of lymphomas in patients with AIDS.

Adult↗

PubMed1994

Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells.

To understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.

Cells, Cultured↗

PubMed1994

Production of interleukin 6 by granulomas of giant cell arteritis.

IL-6 serum levels are increased in patients suffering from GCA, and this cytokine may play a role in the systemic symptoms associated with this disease. We analyzed by in situ hybridization and immunohistochemistry whether IL-6 production originates from arterial granulomas in GCA. Seven arterial biopsy specimens taken from patients with histologically proved GCA were studied. IL-6 production was detected in all cases at both the mRNA and the protein levels. IL-6-producing cells were distributed in the intima, in the media, and in the adventitia. Positive cells were clearly enriched in the media, however, and particularly in contact with the internal elastic lamina. The morphology of the IL-6-producing cells showed that they belonged to several cell populations. In the media, most IL-6-producing cells were macrophages, whereas fibroblasts also produced IL-6 in the intima. Neither endothelial cells nor giant cells were found to express the IL-6 gene. Increased IL-6 serum concentrations returned to normal levels in most patients after administration of corticosteroids, indicating that inhibition of IL-6 production by GCA granuloma cells may be one of the mechanisms of action of corticosteroids in this condition. Production of IL-6 in abnormal arteries may thus participate to the systemic manifestations of GCA.

Aged↗

PubMed1993

Intratumoral production of IL-6 in B cell chronic lymphocytic leukemia and B lymphomas.

Interleukin-6 is a major B lymphocyte growth factor, and may play a role in the proliferation of malignant B lymphocytes. In order to provide arguments supporting such a role, the intratumoral production of IL-6 was studied by in situ hybridization and immunohistochemistry in 53 neoplastic tissues from B cell chronic lymphocytic leukemia or B lymphomas. IL-6-producing cells were detected in all samples but 5. However, the number of IL-6 producing cells was variable amongst the different cases. Increased density of IL-6-producing cells was highly dependent on the presence of malignant immunoblasts within the neoplastic clone. IL-6 was produced in a paracrine way, macrophages and endothelial cells being the main producers of the cytokine while malignant immunoblasts expressed the IL-6 receptor. Taken together, these results suggest that IL-6 may indeed act as a growth factor for malignant cells in some B lymphoproliferations and that this paracrine loop could be the target of new therapeutic approaches.

Gene Expression↗

PubMed1993

[Immunohistochemical study of lesions of temporal arteritis in Horton's disease].

Fourteen monoclonal antibodies were used to immunohistochemically label 22 temporal artery biopsy specimens taken from patients with temporal arteritis before treatment (n = 10), after 1.3 days of corticotherapy (n = 6) and after 12-30 days of steroids (n = 6). Histological sections from untreated patients revealed an inflammatory infiltrate comprised of approximately equal proportions of macrophages and T lymphocytes; the majority of the latter belonged to the CD4+ subset (the CD4+/CD8+ ratio varied from 2/1 to 4/1, depending upon the biopsy). These cells expressed high levels of HLA DR and low levels of interleukin-2 (IL2) receptors. A few B lymphocytes and plasmocytes were seen, mainly in the adventitia. Antigen-presenting cells (APC) were always found in the damaged media and natural killer cells (few in number) were sometimes present. Some macrophages were positively immunolabeled for IL6. A short, 1-to-3-day course of corticosteroids did not appreciably modify the lesions: cells remained highly activated, APC were seen in half the biopsies and IL6 immunolabeling persisted. The findings were essentially the same in treated but poorly controlled patients. Biopsies from 2 patients in clinical and biological remission revealed the persistence of an active immunological process. These observations indicate that the immunological process is poorly controlled by corticosteroid therapy.

Aged↗

PubMed1992

In vivo production of interleukin-10 by malignant cells in AIDS lymphomas.

Expression of the interleukin (IL)-10/BCRF1 gene was studied by in situ hybridization in tissue samples from acquired immunodeficiency syndrome (AIDS) lymphomas using a BCRF1 probe which also recognizes the human IL-10 sequence. Hybridization was detected in 8 out of 15 lymphomas. In contrast, the IL-10/BCRF1 gene expression was detected in only 1 out of 11 lymphomas from human immunodeficiency virus (HIV)-seronegative patients (p = 0.05). In AIDS lymphomas, the number of cells labeled with a BCRF1-specific probe was dramatically lower than that of cells labeled with the IL-10/BCRF1 probe. Thus, the IL-10 rather than the BCRF1 gene was expressed. Production of IL-10 was associated with that of IL-10 mRNA, as shown by immunodetection of the protein in numerous cells. In contrast, BCRF1-producing cells were rarely detected. Both in situ hybridization and immunochemical experiments indicated that malignant cells were involved in this IL-10 synthesis. IL-10 production in AIDS lymphomas was associated with the presence of Epstein-Barr virus (EBV) in lymphomatous cells (p = 0.02). As IL-10 is a potent growth factor for human B lymphocytes, these results suggest that IL-10 may stimulate the proliferation of malignant cells in an autocrine pathway in a number of AIDS lymphomas, and that EBV and HIV may synergistically trigger its production.

Gene Expression↗

PubMed1992

Production of cytokines in sarcoid lymph nodes: preferential expression of interleukin-1 beta and interferon-gamma genes.

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-2, and interferon-gamma (IFN-gamma) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1 beta gene was preferentially expressed. The distribution of cells containing IL-1 beta mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-alpha gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1 alpha gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1 beta gene was significantly higher than that of cells expressing TNF-alpha gene (P = .001), IL-6 gene (P = .007), or IL-1 alpha gene (P less than .001). Of the cells expressing lymphokine genes, those expressing the IFN-gamma gene were 31.9 (+/- 7.6) times more frequent than those expressing the IL-2 gene (P less than .001). Cells containing IFN-gamma mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1 beta gene and the IFN-gamma gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.

Cytokines↗

PubMed1992

Monokine gene expression in normal human liver: selective involvement of the portal compartment.

Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL-1 beta and of IL-6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL-1 beta mRNA or IL-6 mRNA in all cases. Cells expressing either the IL-1 beta gene or the IL-6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL-1 beta gene and of the IL-6 gene may be induced by gut-derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.

Gene Expression↗

PubMed1991

In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients.

We analyzed by in situ hybridization the expression of four interleukin genes (interleukin-beta [IL-1 beta], IL-6, IL-2, and interferon-gamma) in seven thymuses displaying a follicular hyperplasia. The seven thymuses were obtained from patients with myasthenia gravis. Interleukin-1 beta- and IL-6-producing cells were detected in similar amounts and with similar distributions: mainly in perifollicular areas and in the connective structures emerging from the septae at the site of cortex disruption. The comparison of in situ hybridization and immunohistochemical results suggested that thymic epithelial cells and/or perifollicular macrophages were responsible for this production. Interleukin-2-producing cells were detected in perifollicular areas and, to a lesser extent, inside follicles. They were clearly outnumbered by CD25-positive cells which were similarly distributed. Despite the expression of these molecular and immunohistochemical markers of T-cell activation, interferon-gamma-producing cells were extremely rare in myasthenic thymuses. The pattern of interleukin production (which was virtually absent in normal control thymuses) in myasthenic thymuses was different from that in benign hyperplastic lymph nodes. This interleukin production may play a role in the development of follicular hyperplasia in myasthenic thymuses, a phenomenon which is associated with the in situ production of autoantibodies.

Adolescent↗

PubMed1991

Interleukin-2 and interferon-gamma production in follicular lymphomas.

In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low-grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine-synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T-cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction.

Humans↗

PubMed1991

Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients.

Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non-HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1991

[In situ production and possible role of interleukins in clinical immunopathology].

We used in situ hybridization to study the expression of interleukin genes in sarcoidosis and in persistent generalized lymphadenopathy of HIV disease. In both cases, we found a dramatic over-expression of the interferon-gamma (IFN gamma) gene as compared to that of the interleukin-2 (IL-2) gene. In sarcoidosis, IFN gamma producing cells are CD4 T cells and are associated with IL-1 beta gene expressing monocytic cells. In HIV lymphadenopathy IFN gamma producing cells are C8 T cells engaged in cytotoxic function, as evidenced by the concomitant expression of serine esterase B gene. Thus distinct patterns of interleukin production can be defined in vivo in selected immunopathological situations.

HIV Infections↗

PubMed1990

Dual effects of interleukin 4 on antigen-activated human B cells: induction of proliferation and inhibition of interleukin 2-dependent differentiation.

We analyzed the effects of interleukin 2 (IL 2) and IL 4 isolated and in association on the specific response of human B cells triggered by trinitrophenylated polyacrylamide beads (TNP-PAA). IL 2 induced an increase (more than 10 times) in the number of hapten-binding cells [detected by a rosette-forming cell (RFC) assay] as well as the generation of antibody-producing cells [detected by a plaque-forming cell (PFC) assay]. IL 4 induced an isolated RFC response without PFC response. We verified that the IL 4 (as well as 12)-induced RFC were hapten specific and mediated through membrane IgM. Density fractionation experiments showed that IL 4-induced RFC were equally distributed between high-density and intermediate-density B cells. IL 2 appeared to drive more B cells into the intermediate density fraction. IL 2-induced PFC belonged to the RFC population and were intermediate-size B cells. IL 2 drove more RFC into an activated stage and it induced the differentiation of a number of them into antibody-producing cells. The evaluation of the proportion of RFC able to incorporate thymidine showed that both IL induced a substantial proliferation of antigen-activated B cells. However, IL 4 inhibited the IL 2-dependent PFC without affecting the number of RFC nor the proportion of proliferating RFC induced by this IL. These results directly demonstrate that human IL 4 triggers the expansion of antigen-activated B cells and selectively inhibits the IL 2-induced differentiation.

Antibody-Producing Cells↗

PubMed1990

Cystic fibrosis patients' B-lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids.

Cystic fibrosis is associated with an cAMP-regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B-cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co-cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia-delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10(-7) mol l-1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10(-6) mol l-1, whereas this agent induced a dose-related enhancement from 10(-8) to 10(-6) mol l-1 in cultures of normal cells. Co-culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti-CD3 antibody-induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 alpha- or beta-induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.

Adolescent↗