Lymphocytes, lymphokines, and hematopoiesis.

It may be conclusively said that lymphocytes (T cells) produce an array of very powerful hematopoietic peptides, at least one of which (IL-3) appears to be exclusive. All are able to induce proliferation of stem cells of varying commitment, and in combination can reproduce virtually the entire sequence of hematopoietic cell production from the earliest stem cell, for example the HPP stem cells, which responds to T lymphokines in vitro or IL-3 in vivo, to a fully differentiated myeloid cell. Many T lymphokines can be demonstrated to exert highly significant changes in both hematopoiesis and lymphopoiesis in vivo. Thus, IL-3 suppresses NK development, thought to be partly responsible for hybrid resistance, as well as augmenting Ig responses [perhaps through an action on pre-B cells] and stimulating hematopoiesis. The effect on hematopoiesis is probably direct, because infused IL-3 is readily detectable when bound to the surfaces of cells both in the marrow and spleen. It is therefore somewhat surprising that the regulatory role of T cells themselves is less well defined. This arises variously from the availability of purified or recombinant products that replace crude T cell supernates, the complexity of analyzing a multicell system in which very many growth factors cannot be controlled for experimentally, and a certain lag in understanding the basic biology of T cells. This last is perhaps due to the historical recognition of the T cell as an immunocyte, which had led it to be principally investigated in an immunological context. The advent of molecular genetics has resulted in a reappraisal of the interrelationships between many cells, and growth-factor technology has been led to the realization that immune reactivity is perhaps only one function of the T-cell system, and that the classic concept of "immune surveillance" is only a part of a perhaps much wider "surveillance" system in which peptide growth factors and T cells play an exceedingly important role. A pertinent observation concerns abrogation of renal allograft rejection in rats by preoperation injection of donor blood. Although the allografts survive well, the graft is infiltrated by allospecific and nonspecific cytotoxic T cells and expresses donor class I and II antigens in a manner equal to that of a rejecting graft. What, therefore, is the role of lymphokines in this situation--Which of them are expressed, do they activate target cells, and what is the network that controls the macrophages and dendritic cells involved in allograft rejection?(ABSTRACT TRUNCATED AT 400 WORDS)