The potentiation of phytohemagglutinin-induced lymphocyte transformation by cell-cell interaction; a matrix hypothesis

Yachnin, Stanley; Allen, Lawrence W.; Baron, Joseph M.; Svenson, Robert H.

doi:10.1016/0008-8749(72)90120-7

Cited by 46 publications

(26 citation statements)

References 16 publications

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“…In humans, ␥␦ T cells are, however, capable of producing IFN-␥ in response to mycobacterial antigens (40) and they may be responsible for some of the innate IFN-␥ (51). Previous studies on the antigen concentration have estimated the optimal concentration to be 20 g/ml (32), 4 g/ml (1, 29), or 10 g/ml with or without information on previous titration experiments (20,36,46).…”

Section: Discussionmentioning

confidence: 99%

Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

Jungersen

Huda

Hansen

et al. 2002

Clin Vaccine Immunol

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A group of 252 cattle without clinical signs of paratuberculosis (paraTB) in 10 herds infected with paraTB and a group of 117 cattle in 5 herds without paraTB were selected. Whole-blood samples were stimulated with bovine, avian, and johnin purified protein derivative (PPD) and examined for gamma interferon (IFN-␥) release. For diagnosis of paraTB, satisfactory estimated specificities (95 to 99%) could be obtained by johnin PPD stimulation irrespective of interpretation relative to bovine PPD or no-antigen stimulation alone, but numbers of test positives in the infected herds varied from 64 to 112 with different interpretation criteria. For a limited number of test-positive animals, no change in the test results could be observed with increasing antigen concentrations but IFN-␥ responses were significantly reduced (P < 0.0001) and four out of seven reactors tested negative when stimulation was performed on day-old samples. Denmark is free of bovine tuberculosis, but cross-reactivity with paraTB could be documented for cattle more than 14 months old in paraTB-infected herds compared with those in non-paraTB-infected herds. In both paraTB-free and paraTBinfected herds, false positives were observed when the test was applied to calves less than 15 months of age. Until novel antigen formulations more specific for these diseases are available, interpretation of the IFN-␥ test must be individually adjusted to fit specific needs and the context within which the test is applied and, for paraTB, the test seems most appropriate for use as a supportive tool for evaluation of disease-preventive measures in young stock.Paratuberculosis (paraTB) or Johne's disease is a slowly progressive chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (39). In Denmark, paraTB is a serious economic and animal welfare problem with an estimated prevalence of up to 47% in the Danish milk-producing cattle population (26,27). In contrast, the zoonotic bovine tuberculosis (TB), caused by M. bovis, was eradicated in the Danish cattle population half a century ago and control is maintained by meat inspection at slaughterhouses and skin testing of export animals as required.M. avium subsp. paratuberculosis is closely related to the opportunistic pathogen M. avium subsp. avium and also has many antigens in common with M. bovis (16). Although M. avium subsp. paratuberculosis can be cultured from fecal samples, shedding is intermittent until the late stages of infection and growth is exceedingly slow, making diagnostic tests for early diagnosis highly warranted (10). Of the serological assays available, the M. phlei absorbed enzyme-linked immunosorbent assays (ELISAs) are the most sensitive and specific. However, as with other mycobacterial infections, the immune response in paraTB seems to be regulated by a Th1-type cellular immune response well into the progression of the disease (37), which makes serological detection of subclinical cases difficult (38). Assessments of delayed-type hypersensitivity cel...

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Section: Discussionmentioning

confidence: 99%

Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

Jungersen

Huda

Hansen

et al. 2002

Clin Vaccine Immunol

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“…Optimal mitogenic concentrations were evaluated for their agglutinating potential by the method of Yachnin et al (14).…”

Section: Methodsmentioning

confidence: 99%

Guanosine 3′:5′-Cyclic Monophosphate: A Possible Intracellular Mediator of Mitogenic Influences in Lymphocytes

Hadden

Haddox

et al. 1972

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

342

114

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Adenosine 3':5'-cyclic monophosphate (cyclic AMP) has been shown to have an antimitotic role in various cell types, and it has been hypothesized that'a decrease of cyclic AMP concentration in the cell initiates or permits cell division. This hypothesis has been evaluated with respect to clonal proliferation of lymphocytes. Two potent mitogenic agents, phytohemagglutinin and concanavalin A, which induce thymic-dependent lymphocytes to undergo clonal' proliferation, were examined for their ability to initiate proliferation and to alter the concentrations of cyclic AMP and guanosine 3':5'-cyclic monophosphate (cyclic GMP) in purified human peripheral blood-lymphocytes. Optimal mitogenic concentrations of phytohemagglutinin and concanavalin A produced 10-to 50-fold 'increases in the concentration of lymphocyte cyclic GMP within the first 20 min of'exposure to the mitogens. No changes were seen in the concentration of cyclic AMP after stimulation with either mitogen in purified form. Increases of less than 2-fold in 'the concentration of lymphocyte cyclic AMP observed with a less purified preparation of phytohemagglutinin could be attributed to the agglutinating rather than the mitogenic properties of the mitogen. A revised hypothesis' is presented in which a temporally discrete rise in lymphocyte cyclic GMP concentration is viewed as an active signal to induce proliferation, while the elevation of cyclic AMP concentration in these cells is viewed as a regulatory influence that limits or inhibits mitogenic action.The lymphocyte, a cell whose normal functions include, clonal proliferation after stimulation by antigen, provides a model for studying the biochemical events related to initiation of cellular division. Mitogens, such as phytohemagglutinin (PHA) and concanavalin A (Con A), have been used to induce clonal proliferation in lymphocytes, particularly those derived from the thymus. Several experiments (1-6) have been performed in which the relationship between cyclic AMP concentration and mitogen-induced lymphocyte division has been investigated. The results indicate (a) that cyclic AMP itself does not significantly stimulate division of lymphocytes in the resting phase ("Go" or "G1" phase) of the cell cycle (1), (b) that increases in cyclic AMP concentration resulting from stimulation by hormones and polynucleotides do not induce lymphocytes to divide (2, 3), and (c) that agents that promote increases in Iymphocyte cyclic AMP concentration inhibit mitogen-induced clonal proliferation (4-6).Abbreviations: PHA, phytohemagglutinin; Con A, concanavalin A.t To whom reprint requests should be addressed: Box 494 Mayo, University of Minnesota Hospitals, Minneapolis, Minn. 55455.In contrast to the foregoing is the observation that high concentrations of PHA can induce small increases in the amounts of cyclic AMP in lymphocytes (4). These observations have been interpreted as support for the concept that PHA exerts its mitogenic effects through an increase in cellular cyclic AMP concentration. Support for the o...

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“…1 and 2; unpublished data) and is responsible for the mitogenic properties of the isolectins (1)(2)(3)(4)(5). E is responsible for the erythrocyte agglutinating properties (3,6). Isolectin L4 has been termed "leukoagglutinin" (La) (4).…”

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confidence: 99%

Mitogenic leukoagglutinin from Phaseolus vulgaris binds to a pentasaccharide unit in N-acetyllactosamine-type glycoprotein glycans.

Hammarström¹,

Hammarström²,

Sundblad³

et al. 1982

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

133

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The carbohydrate binding specificity of leukoagglutinin (La; Phaseolus vulgaris isolectin L4) was studied by using quantitative precipitation and precipitation-inhibition. A series of purified glycopeptides and synthetic oligosaccharides were used as inhibitors. The minimal structural unit required for La binding was the disaccharide GlcNAc(1-+2)Man. Additions for this basic unit of different sugar residues gave a positive or negative contribution to binding. The most complementary structure was the pentasaccharide Gal(1-.>4)GlcNAc(1-*2)Man 6 Gal(1-*4)GlcNAc. This pentasaccharide unit occurs in tetraantennary N-acetyllactosamine-type glycoprotein glycans. Glycoproteins containing such structures were accordingly precipitated by La. Selected glycopeptides and oligosaccharides were also tested as inhibitors of La-induced DNA synthesis in human lymphocytes. The pattern of inhibition was essentially the same as that obtained by precipitation-inhibition, indicating that binding to lymphocytes via the carbohydrate binding site of the lectin is an essential step in the activation process.

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The potentiation of phytohemagglutinin-induced lymphocyte transformation by cell-cell interaction; a matrix hypothesis

Cited by 46 publications

References 16 publications

Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

Guanosine 3′:5′-Cyclic Monophosphate: A Possible Intracellular Mediator of Mitogenic Influences in Lymphocytes

Mitogenic leukoagglutinin from Phaseolus vulgaris binds to a pentasaccharide unit in N-acetyllactosamine-type glycoprotein glycans.

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