IL-7 (interleukin-7) is a 25 kDa cytokine of the hemopoietin family that plays important roles in lymphocyte differentiation, proliferation, and survival (1?4). Human IL?7 cDNA encodes 177 amino acids (aa) that include a 25 aa signal peptide (3). Human IL-7 shares approximately 60-63% aa sequence identity with mouse, rat, canine and feline IL-7, and 72-76% with equine, bovine, ovine, porcine, feline and canine IL-7. Human and mouse IL-7 exhibit cross-species activity (2, 3). IL-7 protein is produced by a wide variety of cells in primary and secondary lymphoid tissues, including stromal epithelial cells of the thymus, bone marrow, and intestines (1, 2, 5). Circulating IL-7 protein is limiting in healthy animals, but increases during lymphopenia (1, 6). IL-7 signals through a complex of the IL-7 Receptor alpha subunit (IL-7 R alpha, also known as CD127) with the common gamma chain ( gamma?c) (1). The gamma?c?is also a subunit of the receptors for IL-2, -4, -9, -15, and -21 (1). IL-7 R alpha is expressed on double negative (CD4-CD8-) and CD4+?or CD8+single positive na?ve and memory T cells, but undergoes IL-7-mediated down?regulation and shedding during antigen-driven T cell proliferation, and is absent on regulatory T cells (1, 2, 6-11). IL-7 contributes to the maintenance of all na?ve and memory T cells, mainly by promoting expression of the anti-apoptotic protein Bcl-2 (9-11). It is required for optimal T cell-dendritic cell interaction (6). IL-7 is expressed early in B cell development prior to the appearance of surface IgM (1, 5, 9). In mouse, IL-7 activation of IL-7 R alpha is critical for both T cell and B cell lineage development, while in humans, it is required for T cell but not for B cell development (4, 9, 12, 13). However, IL-7 functions in both mouse and human pro-B cells to suppress premature Ig light chain recombination during proliferative growth (14, 15).
