Reviewed are data on the capacity of T lymphocytes to stimulate or inhibit nonlymphoid cell proliferation, on the correlation of this capacity with the activity of respective immunoregulatory cells (T helpers and suppressors), and on the possible cell-mediated and humoral mechanisms through which lymphocytes execute their morphogenic function.
Key Words: proliferation; lymphoid regulation; morphogenetic function; immunoregulatory cellsThe regulation of nonlymphoid cell proliferation by lymphoid cells is central to the broader theory of the regulation by these cells of growth processes in health and disease. The history of studies on this theme may be divided into two periods. During the first period, research efforts were focused on exploring the so-called trophic function of leukocytes, whereby proliferating ceils are supplied with nutrients liberated from leukocytes upon their destruction. Subsequently, emphasis was placed on the morphogenetic function of live lymphocytes, associated with their ability to interact with other cells and to produce biologically active substances and growth factors.As this review is devoted to the morphogenetic function of lymphoeytes, we will only briefly discuss four publications of the first period, since they laid the foundation for lines of research that made important contributions to our knowledge of how lymphocytes regulate cell division [2,3,6,28].The doctrine of lymphocyte trophic function was founded by the well-known French surgeon Alex Carrel [29]. He was the first to call atten- tion to the fact that culturing white blood ceils in protein-free media enriches these with substances of protein nature (trephones) and makes them suitable for culturing cells taken from other, more "capricious" tissues that usually require the addition of embryonal extracts to the medium for their proliferation. Carrel believed that trephones enter the culture medium from disintegrated neutrophils.Substantial contributions to the trophic function doctrine were made by Khrushchov and coworkers [21], who showed that the greatest capacity for stimulating the proliferation of cultured cells was possessed by culture media (leukocytic sera) containing more live than dead cells, irrespective of whether the cells were neutrophils or lymphocytes. These investigators also called attention to the ability of leukocytic sera to suppress, cell division in culture under certain conditions and pointed out the special stimulatory properties of leukocytes contacting cultured cells. The next stage in the evolution of this doctrine was marked by the discovery that lymphocytes making contact with dividing cells in vivo pass some of their nuclear substance on to them. That this is so was indicated by the transfer of 3H-thymidine from the lymphocytes into which it had been incorpo-0007-4888/95/0009-0869512.50 9 1996 Plenum Publishing Corporation