Immune function in aged mice III. Role of macrophages and effect of 2‐mercaptoethanol in the response of spleen cells from old mice to phytohemagglutinin, lipopolysaccharide and allogeneic cells

摘要

AbstractSpleen cells from old mice responded less well to phytohemagglutinin (PHA), lipopolysaccharide (LPS), lipid A and allogeneic cells than those from young mice. The defect in each case resided with the nonadherent responding lymphocyte population rather than adherent accessary cells (macrophages). This conclusion was reached by showing that macrophages from old mice functioned normally in each of their known roles in lymphocyte responsesin vitro; namely, presentation of antigen or mitogen to responding lymphocytes, support of lymphocyte responses and regulation of responses to mitogens and antigens. Normal presentation function was demonstrated by the comparable ability of peritoneal exudate cells from old and young mice to furnish the macrophage requirement for PHA responsivenessin vitro.This conclusion was confirmed by the finding that old, nonadherent cells reconstituted with macrophages from young mice, responded to PHA like unfrationated old cells. Old macrophages were also shown to be normal in their ability to provide the 2‐mercaptoethanol (2ME) replaceable support function to young lymphocytesin vitro.Furthermore, replacement of macrophage supportive activity with 2ME did not rejuvenate the response of old cells to PHA, LPS, lipid A or alloantigens. Finally, no evidence of adherent cell suppression of responses of old cells could be obtained by two different approaches. First, although depletion of adherent cells increased, to a similar degree, the responses ofbothold and young cells to allogeneic stimulation, this procedure did not reduce the difference in responsiveness between them. That is, the decreased response of old cells in a mixed lymphocyte culture (MLC) could not be explained by excessive adherent cell suppression. Second, no evidence for suppression could be obtained in co‐cultures of old and young cells responding to PHA, LPS or allogeneic cells. Taken together, these results suggest that macrophage function, in contrast to lymphocyte function, does not decline with age. It is suggested that this difference may result from the different half‐lives of macrophages and lymphocytes in the intact animal.In contrast to the above results, old spleen cells acting as stimulators in an MLC were not always less effective than young cells. Furthermore, any difference that did exist between young and old cells was largely ablated by depletion of adherent cells. This result suggests that adherent cells from old mice may determine the ability of old cells to stimulate allogeneic lymphocytes in an MLC. It is not known whether this adherent cell is a macrophage or some other adherent (perhaps regulatory)