The Accessory Cell Effects of Liver Macrophages in Concanavalin A Stimulation of Rat Spleen Lymphocytes

Abstract

Liver and peritoneal macrophages under similar test conditions behaved in an identical manner with regard to accessory cell effects in the lymphocyte response to concanavalin A. When present in low concentrations (less than or equal to 3.3%) they stimulate lymphocytes, and when present in high concentrations (greater than or equal to 10%) they inhibit lymphocyte proliferation. These two effects are, however, mediated through totally different mechanisms. Stimulation was an early effect, required viable cells, was not affected by enzymatic treatment of macrophages, and was similar to the effect of 2-mercaptoethanol, allogeneic macrophages, and even non-macrophages. Inhibition occurred at a larger stage of lymphocyte transformation, was sensitive to collagenase and pronase treatment of macrophages, was more specifically due to macrophages, was reduced with allogeneic macrophages, and persisted after freeze-thawing of macrophages. Removal of Fc receptors or related segments of the surface of macrophages greatly reduced their inhibitory capacity, whereas removal of foreign surface receptors apparently had no consequence.

Immunology

“…Mononudear phagocytes are required for T-cell proliferative responses to Con A. This phenomenon has been noted in the mouse (Habu and Raff, 1977;Satoh et al, 1980), rat (Munthe-Kass, 1980), rabbit (Schuyler and Todd, 1980), and man (Raff et al, 1978). Similarly, the T-cell lymphoproliferative responses to PHA exhibit a mononudear-phagocyte dependence in mice Habu and Raff, 1977;Satoh et al, 1980) and guinea pigs (Gorenberg and Daniele, 1978;Rogoff and Lipsky, 1979).…”

Promotive and Inhibitory Effects of Macrophages on the Mitogen‐induced Blastogenesis of Lymphocytes: A Flow‐cytometric Study

“…This observation may indicate that the presence of macrophages leads to production of an inhibitory factor that bebecomes cytotoxic when it reaches a certain concentration. Apparently, this factor is not produced by the macrophages themselves, since the inhibitory elTect was retained after freezethawing of these cells [14] and even by partly purified macrophage membranes [18,19], A possible candidate for such a factor is complement. Thus, the inhibitory cfTects of macrophages are similar to those of hyperoptimal concentrations of Con A and other mitogens.…”

“…Non-adherent spleen lymphoeytes from rals were prepared as described in detail elsewhere [14] and suspended in RPMMMO containing 15",, autologous serum.…”

“…28]. The promotive effect appears to i>e unspecific in the sense that various other cell types, such as fibroblasts [13], have a similar effect, as have also dead cells and cell lysates [14]. Promotion is also effected by 2-mercaptoethanol (2-ME) and some other tiols [II.…”

“…17]. In contrast, the inhibitory effect is seen only with macrophages and is much more pronounced when Ihese cells are syngeneic to the lymphocytes [14].…”