Biological and clinical implications of interleukin-7 and lymphopoiesis.
Interleukin 7 (IL-7) is a stromal cell-derived cytokine that stands out as being the only cytokine identified to date on which development of B and T lymphocytes is absolutely dependent. IL-7 functions primarily as a growth and antiapoptosis factor for B- and T-cell (alphabeta and gammadelta TCR+ cells) precursors, and is essential for differentiation of gammadelta TCR+ cells. IL-7 can function as a cofactor during myelopoiesis, and is capable of activating monocytes/macrophages and natural killer (NK) cells. Its receptor (IL-7R) is a heterodimer of an alpha chain that specifically binds IL-7 and the common gamma chain gammac that is also a component of the receptors for IL-2, IL-4, IL-9 and IL-15. The functions of IL-7 in normal lymphocyte development and activation have led to the demonstration of the ability of IL-7 to stimulate lymphopoiesis in lymphopenic mice, suggesting a possible clinical application of IL-7 in accelerating lymphoid reconstitution in lymphopenic patients. There have also been a number of preclinical studies pointing to the possible utility of IL-7 in antitumor clinical applications, and clinical trials involving IL-7 gene therapy of metastatic disease are underway. IL-7 has also been shown to promote engraftment of stem cells in mice receiving bone marrow transplants, pointing to a possible use of IL-7 in patients receiving bone marrow or peripheral blood stem cell transplants. Areas of IL-7 biology that are essentially unexplored include the mechanisms of regulation of the expression of IL-7 and IL-7Ralpha, as well as the mechanisms by which IL-7 is a growth and differentiation factor for gammadelta T cells but a growth factor only for alphabeta T cells.
Appasamy
P M
PM
University of Pittsburgh Cancer Institute and Department of Pathology, University of Pittsburgh School of Medicine, PA 15213, USA. gastro@pop.pitt.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D020395:Receptors, Interleukin-7 / Q000737:chemistry; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015851:Interleukin-7; D020395:Receptors, Interleukin-7