Modulation of immunity by macrophages

The literature concerning the effects of macrophages on the immune response is already large and growing rapidly. Macrophages seem to be involved in almost every phase of the immune response. Not only are they important as effector cells in their own right, but there is now a wealth of information suggesting macrophages may, through a combination of suppressing and enhancing effects, play an important role in regulating the immune response. Evidence obtained both in vivo and in vitro supports the concept of macrophages as immunoregulatory cells. We shall review here the available in vivo and in vitro evidence for augmentation and suppression of immune response by macrophages, and will also suggest how macrophages may play a role as effector cells in T cell suppression and antigenic competition. Many of the in vitro experiments, on which important conclusions have been based, have compared the results obtained in assay systems using cell populations depleted of macrophages to those obtained using cell populations containing, or highly enriched for, macrophages. Before discussing the details of these experiments, it is important to note that there are problems with interpreting such data. There is virtually no way to prepare cell populations completely free of macrophages. None of the available methods have been shown to reduce the proportion of macr0phages below 0.1 per cent, and this may not be sufficient to rule out the role of very small numbers of macrophages as auxiliary cells for the induction of immune responses. Most of the macrophage depletion procedures are based on adherent or phagocytic properties of macrophages. Petri dish adherence (Mosier, 1967) allows separation of the cells into two populations which can be tested alone or after recombination. The resultant populations, however, are by no means pure and the degree of depletion of macrophages is not as good as that achieved by other techniques. Passage of lymphoid cells over adherence columns of nylon wool (Julius et al., 1973), rayon cotton (Kirchner et al., 1974b), glass beads (Shortman, 1968), or Sephadex G-10 (Ly and Mishell, 1974) allows rather good depletion of adherent cells. However, since B cells are adherent, albeit less than macrophages, those procedures most effective in depleting adherent cells must of necessity deplete a certain proportion of the B cells. In fact, a procedure based on this principle has been described to obtain a purified population of T cells simply by depleting all of the adherent cells (Julius et al., 1973). Since, however, as many as 80 per cent of the cells are lost when performing such procedures, it is obvious that even some T cells are depleted. In addition to the separation procedures based on the adherent properties of macrophages, incubation of cells with powdered iron to allow phagocytic cells to ingest the iron particles, and then passage of the cells through a strong magnetic field to obtain a population free of phagocytes (iron and magnet technique), has been a useful technique to obtain a phagocyte-depleted population (Kirchner et al., 1974b). However, since the percentage of the cells recovered (50-60 per cent of normal spleen cells) is routinely lower than the percentage of cells which are non-phagocytic, it is clear that even this depletion technique is not entirely selective for macrophages. Another approach to the problem of obtaining purified cell populations has been the