An overview of IL-7 biology and its use in immunotherapy.

Abstract

Interleukin (IL)-7 is required for T-cell development as well as for the survival and homeostasis of mature T-cells. In the thymus, the double negative (DN) CD4(-) CD8(-) thymocyte progenitor transition into double positive CD4+ CD8+ cells requires Notch and IL-7 signaling. Importantly, IL-7 seems to have a dose effect on T-cell development and, at high doses, DN progression is blocked. Naïve T-cells in the thymus, and after their exit to the periphery, are dependent on IL-7 and TCR signaling for survival. Upon antigen exposure, they proliferate and differentiate into memory T-cells. Because IL-7 intervenes at all stages of T-cell development and maintenance, it has been introduced recently into clinical trials as an immunotherapeutic agent for cancer patients (of particular note, those who had undergone T-cell depleting therapy) in an attempt to increase their population sizes of CD4+ and CD8+ cells overall, and specifically of CD8+ (CD45RA+)CCR7+ and/or CD27+), CD4+ (CD45RA+CD31+), and CD4+ central memory T-cells (CD45RA(-)CCR7+). Interestingly, IL-7 in humans induced a preferential expansion of naïve T-cells, resulting in a broader T-cell repertoire than before the treatment; this effect was independent of age. This suggests that IL-7 therapy could enhance immune responses in patients with limited naïve T-cell numbers as in aged patients or after disease-induced or iatrogenic T-cell depletion. This overview highlights the role of IL-7 on T-cells in mice and humans.

• Authors: Nahed ElKassar, Ronald E Gress
• Journal: Journal of immunotoxicology (J Immunotoxicol) Vol. 7 Issue 1 Pg. 1-7 (Mar 2010) ISSN: 1547-6901 [Electronic] England
• PMID: 20017587 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Interleukin-7

Topics

• Animals
• Antibodies, Monoclonal
• Cell Differentiation (drug effects, immunology)
• Humans
• Immunity, Cellular (drug effects, immunology)
• Immunotherapy (methods)
• Interleukin-7 (administration & dosage, immunology, metabolism)
• Lymphocyte Activation
• Mice
• Models, Animal
• Neoplasms (immunology, therapy)
• Signal Transduction (drug effects, immunology)
• T-Lymphocytes (cytology, drug effects, immunology)
• Thymus Gland (growth & development, immunology, metabolism)