Increased production of IL-7 accompanies HIV-1–mediated T-cell depletion: implications for T-cell homeostasis

Abstract

We hypothesized that HIV-1-mediated T-cell loss might induce the production of factors that are capable of stimulating lymphocyte development and expansion. Here we perform cross-sectional (n = 168) and longitudinal (n = 11) analyses showing that increased circulating levels of interleukin (IL)-7 are strongly associated with CD4+ T lymphopenia in HIV-1 disease. Using immunohistochemistry with quantitative image analysis, we demonstrate that IL-7 is produced by dendritic-like cells within peripheral lymphoid tissues and that IL-7 production by these cells is greatly increased in lymphocyte-depleted tissues. We propose that IL-7 production increases as part of a homeostatic response to T-cell depletion.

Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vγ9Vδ2 naive, memory and effector T cell subsets

“…Although the relative contributions of different cytokines to homeostatic proliferation in humans are difficult to address directly, recent reports are consistent with the view that human and murine T cells have similar requirements [13,14,21,[28][29][30][31][32]. Thus, antigen-independent naive T cell proliferation in the mouse requires TCR tickling, IL-7, and lymphopenia, whereas CD8 memory T cells turn over constitutively, express high levels of the IL-2/ 15Rb chain and require IL-15 or IL-7.…”

IL‐7Rα expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation

“…Under normal conditions, when there is a reduction of T cell numbers in the periphery, levels of IL-7 increase to send survival signals via the IL-7R to promote antigen independent, or homeostatic proliferation to rebalance T cell numbers [16,44]. In lymphopenic HIV-infected individuals, there is an elevated level of IL-7 caused by the homeostatic response to T cell depletion [45,46]. However, if the expression of IL-7Ra is reduced in HIV-positive individuals, as we have shown here, this increased production of IL-7 to promote homeostatic rebalance may be ineffective.…”

Acute Thymic Involution and Mechanisms for Recovery

“…The clinical application of IL-7 not only leads to enhanced proliferation and increases in the number of T cells but also causes alterations in the peripheral T cell subsets and the diversification of the T cell receptor repertoire (Mackall et al 2011). During HIV-1 infection, the production of IL-7 is amplified to maintain homeostasis in response to T cell depletion (Napolitano et al 2001). The exogenous administration of IL-7 enhances the regeneration of the T cells after transplantation of bone marrow, and its positive effect on immune reconstitution is associated with a considerable increase in thymopoiesis (Mackall et al 2001).…”