IL-7 induces functional activation of α4β7 and migration of naive human T cells to the intestinal compartment in humanized NSG mice. (A) Binding of the specific α4β7 ligand MAdCAM-1 to purified memory and naive CD4⁺ T cells treated for 24 hours with the indicated cytokines or left untreated. The shaded histograms denote the staining of cytokine-treated cells; the empty profiles denote the staining of control, untreated cells; the red hatched histograms denote staining in the presence of the neutralizing anti-α4 mAb HP2/1. Data are representative of 3 independent experiments performed with similar results. (B) Expression of integrin α4β7 in T cells derived from the blood, spleen, inguinal lymph nodes (iLN) and mesenteric lymph nodes (mLN) of wild-type C57BL/6 mice injected subcutaneously with murine IL-7 (1 or 5 μg/mouse) or treated with placebo (control). Mean values (± SEM) from 2 mice tested for each condition are shown. (C) Tissue homing of IL-7–treated naive and memory human T cells injected into humanized NSG mice. Human CD4⁺ T cells purified from healthy blood donors and treated ex vivo with IL-7 for 48 hours were loaded with a vital dye, mixed at 1:1 ratio with untreated autologous cells loaded with a different vital dye, and then injected into the tail vein of 6 NSG mice previously repopulated with autologous PBMCs. After 18 hours, the mice were killed, and the relative proportion of IL-treated versus untreated cells was quantitated in blood and peripheral tissues. Naive and memory T cells were separately analyzed by differential gating based on the expression of human CD45RA and CD45RO. The data indicate the mean percent increase (± SEM) in the number of recovered IL-7–treated cells over untreated cells for the indicated T-cell subset from the tissues of 6 mice. Statistical analysis was performed using a Wilcoxon matched-pairs test. The numbers in parentheses denote the proportion of total naive and memory human T cells recovered in the indicated tissue.