Defective production of monocyte-activating cytokines in lepromatous leprosy.

Horwitz, Marcus A.; Levis, William R.; Cohn, Zanvil A.

doi:10.1084/jem.159.3.666

Cited by 45 publications

(20 citation statements)

References 15 publications

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“…This confirms previous reports (11-13) on the presence of a BCG-reactive T cell population in patients unable to respond to M. leprae. T cells from all patients proliferated in response to Con A as reported (9). Therefore, the T cell defect in lepromatous disease is specific for M. leprae but is manifested as both nonresponsive and hyporesponsive states.…”

Section: Kaplanmentioning

confidence: 74%

“…lepromin antigens as well as an absence of T cell proliferation and lymphokine release in vitro (8,9,11,12). However, patients exhibit responsiveness to mitogenic lectins and to the M. leprae-related organism, BCG, irrespective of their ability to respond to M. leprae.…”

Section: Effect Of T Cell and Monocyte Depletion On The Proliferativementioning

confidence: 99%

“…The exposure of peripheral blood T cells to M. leprae fails to result in appreciable T cell proliferation and synthesis of lymphokine, including IFN-3" (8-10). In contrast, the lymphocytes of patients with lepromatous leprosy can respond to l~ctins and other antigens to which they are sensitized (4,(8)(9)(10)(11)(12)(13). This had lead to the concept of selective anergy in which, either due to the absence ofM.…”

mentioning

confidence: 99%

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An analysis of in vitro T cell responsiveness in lepromatous leprosy.

Kaplan¹,

Weinstein²,

Steinman³

et al. 1985

The Journal of Experimental Medicine

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Antimicrobial defense mechanisms are enhanced by antigen-specific T cell differentiation followed by activation of mononuclear phagocytes (1, 2). 3" Interferon (IFN-3,) ~ is an important mediator of both antimicrobial activity and hydrogen peroxide secretion in mononuclear phagocytes (3). A number of observations suggest that an immunological defect exists in lepromatous leprosy w_hich-allows the extensive replication of M. leprae within dermal macrophages (4). The skin lesions are relatively deprived of helper T cells (OKT4), which are an important source of IFN-3" (5-7). The exposure of peripheral blood T cells to M. leprae fails to result in appreciable T cell proliferation and synthesis of lymphokine, including IFN-3" (8-10). In contrast, the lymphocytes of patients with lepromatous leprosy can respond to l~ctins and other antigens to which they are sensitized (4,(8)(9)(10)(11)(12)(13). This had lead to the concept of selective anergy in which, either due to the absence ofM. leprae-reactive T cells and/or the activity of suppressor cells or factors, macrophage activation does not occur and microbial dissemination ensues (1 1-23).In the course of studies on the reversal of T cell nonresponsiveness with purified IL-2 in lepromatous leprosy patients (8), we were struck by the heterogeneous response to this T cell growth factor. We have therefore reexamined the responsiveness of T cells to M. leprae and other antigens, and evaluated their stimulation by recombinant IL-2 and their possible inhibition by suppressor cell populations. Materials and MethodsPatients. Patients (see Table I Abbreviations used in this paper: BCG, bacillus Calmette Guerin; C*, rabbit complement; Con A, concanavalin A; IFN-3,, immune (gamma) interferon; IL-2, interleukin 2; mAb, monoclonal antibodies.J. ExP. MED.

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Section: Kaplanmentioning

confidence: 74%

Section: Effect Of T Cell and Monocyte Depletion On The Proliferativementioning

confidence: 99%

mentioning

confidence: 99%

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An analysis of in vitro T cell responsiveness in lepromatous leprosy.

Kaplan¹,

Weinstein²,

Steinman³

et al. 1985

The Journal of Experimental Medicine

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“…If human monocytes from patients with leprosy are activated with supernatants from concanavalin A-stimulated lymphocytes, the monocytes inhibit the intracellular replication of L. pneumophila (136). Similarly, when a cellular immune response is produced in the lung by infection with mycobacteria, increased resistance to inhaled L. pneumophila results (111).…”

Section: Microbiology and Immunologymentioning

confidence: 99%

Legionnaires disease: historical perspective

1988

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In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.

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“…In studies of blood cells from lepromatous leprosy patients, Zan and colleagues outlined a deficiency in the production of IFN-3~ and macrophage-activating cytokines following challenge with M. teprae antigens (228,243). When they found that low levels of responsiveness in T cells from some patients could be boosted by interleukin 2 (IL-2) (254), they turned to reversing the deficit in situ.…”

Section: Manipulating Cell-mediated Immunity With Lymphokines In Humamentioning

confidence: 99%

Zanvil Alexander Cohn 1926-1993.

Steinman¹,

Moberg²

1994

The Journal of Experimental Medicine

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SummaryZanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of thisJournaI, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn's collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease. He guided with a warm but incisive manner the careers of many individuals. He was deeply committed to several institutions of biomedical research; to medicine in the developing world; to The Rockefeller University, especially its programs for graduate study and patient-oriented research;and to the energy and spirit of this Journal.

show abstract

Defective production of monocyte-activating cytokines in lepromatous leprosy.

Cited by 45 publications

References 15 publications

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

Legionnaires disease: historical perspective

Zanvil Alexander Cohn 1926-1993.

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