The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

Kaplan, Gilla; Laal, Suman; Sheftel, Giulia; Nusrat, Asma; Nath, Indira; Mathur, N. K.; Mishra, Rabinarayan; Cohn, Zanvil A.

doi:10.1084/jem.168.5.1811

Cited by 44 publications

(25 citation statements)

References 26 publications

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“…Careful evaluation of the number of acid-fast bacilli from skin sites biopsied up to 7 days after one to three injections of lymphokine suggested some reduction in the bacillary indices (BIs). However, this was often patchy in nature and not as striking as that occurring after the administration of the lymphokine interleukin 2 (IL-2) or purified protein derivative of tuberculin (PPD) to sensitized lepromatous patients (8,9).…”

mentioning

confidence: 99%

Effect of multiple interferon gamma injections on the disposal of Mycobacterium leprae.

Kaplan

Mathur

Job

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The effect of multiple intradermal injections (four to six) of 10 pg of interferon y on the number of Mycobacterium leprae in the skin of patients with polar lepromatous leprosy and borderline lepromatous leprosy was evaluated. To achieve a maximum zone of induration and cell emigration a preparatory dose ofthe lymphokine was required.A second group of three injections, given 3-4 days after the initial series, resulted in lesser degrees of induration and was more in keeping with a partial local hyporesponsive state. A marked emigration of T cells and monocytes into the dermis resulted from injections of interferon y and persisted for >21 days. A preponderance of CD4' cells in the infiltrate was seen within a few days and CD4/CD8 ratios remained elevated for >3 weeks. The bacillary load of injected sites evaluated 21 days after lymphokine administration was reduced in 14/17 patients by factors ranging from 5-to 1000-fold. This occurred predominantly within diffuse lesions and occurred rarely in nodular sites. Biopsy samples of injected sites taken 6 months later demonstrated progressive 10-fold reductions in bacilli and the continued presence of a granulomatous response.

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mentioning

confidence: 99%

Effect of multiple interferon gamma injections on the disposal of Mycobacterium leprae.

Kaplan

Mathur

Job

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…For this purpose injection of PPD alone or in the presence of nonviable M. leprae was carried out. As noted previously, the response to PPD in sensitized human skin includes an emigratory event (17), the generation of primary and secondary cytokines (26), and complex responses of endothelium, fibroblasts, Langerhans cells, and keratinocytes (27,28).…”

Section: Resultsmentioning

confidence: 99%

“…Biopsy specimens were fixed in phosphate-buffered saline containing 3% paraformaldehyde, 75 mM lysine, and 10 mM sodium metaperiodate (20) and were processed as described (18). Frozen sections were stained with mouse monoclonal antibodies as described (17) to identify cell types and phenotypes.…”

Section: Methodsmentioning

confidence: 99%

“…We have quantitated suppression by virtue of the ability of these agents to modify the area of induration evoked by a reaction to the purified protein derivative of tuberculin (PPD) (17) or by the injection of recombinant IL-2, a lymphokine that mimics a cell-mediated immune reaction (18). In other experiments either antigen or IL-2 was administered first and was followed 1-4 days later by the complementary antigens or IL-2 into the same site.…”

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Influence of Mycobacterium leprae and its soluble products on the cutaneous responsiveness of leprosy patients to antigen and recombinant interleukin 2.

Kaplan¹,

Sampaio²,

Walsh³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Experiments were carried out in the skin of patients with leprosy to examine whether suppressor cell populations either exist in the skin of multibacillary lepromatous leprosy patients, can be activated with antigen, or are induced to emigrate into a cutaneous site from the circulation. For this purpose, purified protein derivative of tuberculin, a delayed-type antigen that generates a cell-mediated immune response, was introduced into the skin alone or with nonviable Mycobacterium leprae bacilli. Areas of induration and the resulting numbers and phenotypes of emigratory cells were not influenced by M. leprae and its products. Further studies examined the ability of M. leprae and its soluble products to modify the cutaneous response to intradermal injection of recombinant interleukin 2 (IL-2), a lymphokine that mimics a cell-mediated response. Neither the simultaneous injection of M. leprae and IL-2, nor the prior injection ofM. leprae followed in 2 days by IL-2, nor the prior aIministration of IL-2 followed in 4 days by M. leprae, into the same skin site, modified the zone of induration generated by IL-2. In addition, the immunocytochemical and histopathological evaluation of biopsy specimens of skin sites showed no difference between sites injected with IL-2 and sites injected with IL-2 and M. leprae. We conclude that suppressor T cells, if they exist, do not influence the gross or microscopic responsiveness of a cell-mediated skin reaction to antigen and IL-2. IL-2 did, however, enhance the responsiveness of skin-test-positive tuberculoid patients and family contacts to M. leprae antigens by a synergistic effect on the zone of induration and local cell accumulation.

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“…Although lepromatous patients are unresponsive to the lepromin antigen from M. leprae, the patients can exhibit a typical DTH response to the tuberculin skin test antigens from M. tuberculosis (325). Kaplan, Cohn, and colleagues noted a substantial decrease in acid fast bacilli at the DTH site (326).…”

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

The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

Cited by 44 publications

References 26 publications

Effect of multiple interferon gamma injections on the disposal of Mycobacterium leprae.

Effect of multiple interferon gamma injections on the disposal of Mycobacterium leprae.

Influence of Mycobacterium leprae and its soluble products on the cutaneous responsiveness of leprosy patients to antigen and recombinant interleukin 2.

Zanvil Alexander Cohn 1926-1993.

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