Effects of Increasing IL-7 Availability on Lymphocytes during and after Lymphopenia-Induced Proliferation

Abstract

IL-7 is critically involved in regulating peripheral T cell homeostasis. To investigate the role of IL-7 on lymphopenia-induced proliferation of polyclonal lymphocytes, we have transferred CFSE-labeled cells into a novel T-lymphopenic, IL-7-transgenic mouse line. Results obtained indicate that T and B cells do not respond in the same way to IL-7-homeostatic signals. Overexpression of IL-7 enhances proliferation of both CD4+ and CD8+ T cells but with distinctly temporal effects. Expansion of naturally arising CD4+-regulatory T cells was like that of conventional CD4+ T cells. IL-7 had no effect on B cell proliferation. By immunohistology, transferred T cells homed to T cell areas of spleen lymphoid follicles. Increasing IL-7 availability enhanced T cell recovery by promoting cell proliferation and reducing apoptosis during early stages of lymphopenia-induced proliferation. Taken together, these results provide new insights into the pleiotropic effects of IL-7 on lymphopenia-induced T cell proliferation.

IL-2 and IL-7 Determine the Homeostatic Balance between the Regulatory and Conventional CD4+ T Cell Compartments during Peripheral T Cell Reconstitution

“…Altogether, our results suggest that IL-7R expression on regulatory CD4 + T cells may be too low to enable them to respond to the IL-7 levels reached in a lymphopenic environment. In line with this hypothesis, it was shown that regulatory CD4 + T cells are able to proliferate in vivo in response to the high levels of IL-7 reached in IL-7-transgenic mice or in mice injected with high concentrations of exogenous IL-7/anti-IL-7 complexes (41,42).…”

Peripheral T Lymphocytes Recirculating Back into the Thymus Can Mediate Thymocyte Positive Selection

“…Clearly, during an ongoing antiviral immune response, some degree of priming is seen among mature thymocytes (25,26). Using either parabiosis (6) or transfer of CFSE-labeled cells (27), we have previously shown that in a situation of peripheral lymphopenia, the contribution of recirculating peripheral T cells to the pool of mature "thymocytes" was significant. Using complementary approaches, including adoptive transfer of genetically marked T cells and the intrasplenic injection of CFSE, in this study we quantify this recirculation in detail and analyze the phenotype and TCR V␤ repertoire of recirculating cells.…”

IL-7 administration drives T cell–cycle entry and expansion in HIV-1 infection

“…3,[8][9][10][11] In animal models of lymphopenia, administration of IL-7 can facilitate restoration of lymphocyte homeostasis even in the presence of high serum levels of IL-7 and low T-cell IL-7 receptor levels. 12 Despite its central role in B-cell lymphopoiesis in the mouse, the role of IL-7 in human B-cell lymphopoiesis is not considered essential. 3,13 The fundamental roles of IL-7 in thymopoiesis, maturation, survival, and differentiation of T cells provided the rationale for testing this cytokine as an immune adjuvant therapy in HIV infection.…”