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

Abstract

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.

Spontaneous and Concanavalin A-induced suppressor activity in control and Hodgkin's disease patients

“…Our results with T-enriched spleen cell fractions show that this is also the case in spleen. Spontaneous suppressor activity, attributed in the blood to the spontaneous activation of suppressor cells under culture conditions (Schwartz et al, 1977) was apparent in mitogen-free cultures of cells from HD and control spleens. It is also clear from these results that there is a reciprocal relationship between spontaneous suppression and that induced by Con A, suggesting that in' both cases the activated cell represents identical or overlapping populations.…”

“…The levels of inhibition of Ig synthesis observed with both peripheral blood and splenic suppressor cells were similar. Several authors have described a range of effects on PWM activation mediated by peripheral blood lymphocytes in culture, ranging from stimulation to marked suppression (Schwartz et al, 1977;Lipsky et al, 1978). Our results with T-enriched spleen cell fractions show that this is also the case in spleen.…”

“…Con A activates a heterogeneous pool of cells (Damle & Gupta, 1982) within which distinct subpopulations of induced suppressor cells regulate immunoglobulin (Ig) synthesis and proliferation in mixed lymphocyte culture (Lobo & Spencer, 1979;Herscowitz et al, 1980). When pokeweed mitogen (PWM) induced Ig synthesis is used to assay for Con A-induced suppression, control as well as Con A-induced cells may exert inhibitory activity (Schwartz et al, 1977; Haynes Lipsky et al, 1978). This "spontaneous" suppressor activity of control cells is thought to reflect the expansion of a pre-existent inhibitory cell sub-population in vitro (Lipsky et al, 1978).…”

“…The lectin Concanavalin A (Con A) has been extensively used as a tool for the study of immunoregulation in man (Shou et al, 1976;Smith & Svejgaard, 1981;Dwyer & Johnson, 1981). The inhibitory activity induced by this mitogen is considered to be a normal functional characteristic of T-cells, loss of which may be associated with various autoimmune phenomena Sakane et al, 1978).…”

In Vitro Immune Response of Human Peripheral Lymphocytes

“…suppressor and helper (10,23). In humans, Con A-stimulation generated suppressor T cells which inhibited mitogen-or alloantigen-induced proliferation of T cells (18) or PWM-induced Igproduction (7,17). Since it is assumed that Con A activates the precursors committed to helper or suppressor cells into helper or suppressor T cells, the quantitation of Con A-generated suppressor T cells may be an useful approach to estimate the regulatory functions of T cells in human beings.…”