Hodgkin's disease. An immunodepleting and immunosuppressive disorder.

Twomey, Jeremiah J.; Laughter, Arline H.; Farrow, S; Douglass, Charles C.

doi:10.1172/jci108113

Cited by 194 publications

(57 citation statements)

References 38 publications

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“…These cells have been suggested as etiologic or contributory in the pathogenesis of several diseases, including common variable hypogammaglobulinemia (43), IgA deficiency (44), multiple myeloma (45), Hodgkin's disease (11,40,46), and systemic lupus erythematosus (47). Work in this area has been hindered, however, by lack of a suitable assay of suppressor cell activity.…”

Section: Discussionmentioning

confidence: 99%

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Goodwin¹,

Bankhurst²,

Messner³

1977

The Journal of Experimental Medicine

724

120

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Prostaglandins (PGs) I of the E series have been shown to inhibit many in vitro measurements of immune function in experimental animals. These include macrophage inhibitory factor production in guinea pigs (1, 2), direct cytolysis in murine lymphocytes (3), hemolytic plaque formation by murine leukocytes (4), and mitogen-induced stimulation of murine lymphocytes (5). In the human, Lomnitzer et al. (6) have shown that PGEI and PGE2 cause reduction in leukocyte inhibitory factor production by phytohemagglutinin(PHA)-stimulated human lymphocytes. Smith et al. (7) demonstrated significant inhibition of [3H]thymidine incorporation into PHA-stimulated human lymphocytes by PGEI, E2, At, and F~. As in the study by Lomnitzer, the final concentration of PGs was relatively high, I0-~-I0-4M. Ferraris and Derubertis have reported (8) that stimulation of 10 ~ human luekocytes with optimal concentrations of PHA produced -10-8M PGE.These data suggest that PGs of the E series might act as endogenous modulators in human immune reactions. PGEI is produced in the mitogen stimulation of human leukocytes, and may in turn inhibit this stimulation. Thus, data are accumulating to support the hypothesis of Bourne et al. (9) that PGs are important regulators of immune function. One troublesome aspect of the studies on human leukocytes is the great disparity between the amount of PGE produced during mitogen stimulation (~10-SM or 5 ng/ml) and the amount required to suppress mitogen stimulation when added to cultures (~10-5M or 5 pg/ml).In the present paper we describe the effects of lower, more physiologic concentrations of PGs on mitogen stimulation of human lymphocytes and lymphocyte subpopulations. We also describe the effect of PG synthetase inhibitors on mitogen-induced stimulation of these cells. We have identified a population of glass adherent mononuclear cells that suppress T-cell mitogenic activity through production of PGs of the E series.

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Section: Discussionmentioning

confidence: 99%

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Goodwin¹,

Bankhurst²,

Messner³

1977

The Journal of Experimental Medicine

724

120

View full text Add to dashboard Cite

show abstract

“…Triplicate cultures were prepared in flat-bottomed microtiter plates (Linbro Chemical Co., New Haven, Conn.) and incubated for 7 days (except where specified otherwise). Our leukocyte culture technique, the preparation of mitogens and antigens, and the method employed to measure [3H]thymidine incorporation have been described elsewhere in detail (10)(11)(12). Proliferative stimuli tested included phytohemagglutinin (PHA) (Difco Laboratories, Detroit, Mich.), pokeweed mitogen (Grand Island Biological Co., Grand Island, N.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of lymphoproliferation by hyperlipoproteinemic plasma.

Waddell¹,

Taunton²,

Twomey³

1976

J. Clin. Invest.

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A B S T R A C r['H]-Thymidine incorporation correlated well with morphologic evidence of lymphoproliferation. The mechanism of the inhibitory effect of type IV or V hyperlipoproteinemic plasma upon the response tested was not identified but may be related to interaction between lipoproteins and the cell membranes. We suggest that these lipoproteins may also interfere with the function of other cells.

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“…Moreover, a degree of genetic identity appears to be required for the expression of "weak" immunoregulatory influences. Although immunologically active suppressor cells have been associated with several disease states in human beings (1)(2)(3)(4)(5), we have recently demonstrated that suppressor cell activity can also be induced in lymphocytes from healthy donors (6). This activity involved inhibition of functions associated with thymus-derived lymphocytes (T-cells), namely, blast transformation responses to mitogens, allogeneic stimulation, and certain antigens.…”

mentioning

confidence: 99%

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Schwartz¹,

Shou²,

Good³

et al. 1977

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

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Concanavalin A (Con A)treated peripheral blood lymphocytes from healthy volunteer donors have been shown to suppress proliferative responses associated with thymusderived lymphocytes (T-cells). The present investigations demonstrate that peripheral blood lymphocytes incubated with Con A for 48 hr can abrogate pokeweed mitogen-stimulated differentiation of bone-marrow-derived (B) lymphocytes to immunoglobulin-synthesizing and -secreting plasma cells. This effect was manifested when washed Con A-treated peripheral blood lymphocytes were added to pokeweed mitogen-stimulated cocultures containing fresh autologous or allogeneic mononuclear cells, and it did not appear to involve cytotoxicity. Parallel control cultures consisting of mononuclear leukocytes incubated for 48 hr in the absence of Con A also had immunoglobulin suppressor activity in mixing experiments. This effect, however, was most pronounced when preincubated cells were added to fresh autologous pokeweed mitogen-stimulated peripheral blood lymphocytes. Cell mixtures containing peripheral blood lymphocytes incubated in the absence of Con A plus fresh allogeneic lymphocytes demonstrated a spectrum of immunoregulatory effects ranging from suppression to enhancement of pokeweed mitogen-stimulated immunoglobulin synthesis and secretion. Several functional subclasses of suppressor cells that reflect varying levels of specific activity have thus been demonstrated in human beings. Moreover, a degree of genetic identity appears to be required for the expression of "weak" immunoregulatory influences.

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Hodgkin's disease. An immunodepleting and immunosuppressive disorder.

Cited by 194 publications

References 38 publications

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Inhibition of lymphoproliferation by hyperlipoproteinemic plasma.

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

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