Figure 1

BLT humanized mice exhibited a profound loss of human CD4⁺T cells/thymocytes following HIV-1 _LAI infection. (A-B) Three cohorts of BLT humanized mice were exposed intravenously to increasing doses of HIV-1_LAI (LAI). LAI inoculations included a low dose of 3000 TCIU (triangles), an intermediate dose of 30,000 TCIU (circles), and a high dose of 600,000 TCIU (diamonds). A fourth cohort consisted of naïve BLT humanized mice that were not exposed to virus (squares). Longitudinal analysis of plasma viral load revealed efficient viral replication in each of the three groups of LAI infected mice regardless of the inoculation dose, and no virus replication was observed in the naïve animals (A). In the absence of infection in naïve BLT humanized mice, the percentage of human CD4⁺ T cells in the peripheral blood remains constant. In contrast, LAI infected mice showed an inoculation dose dependent difference in the kinetics of CD4⁺ T cell loss. Asterisks represent the absence of detectable levels of peripheral blood human CD4⁺ T cells in the BLT humanized mice infected with 600,000 TCIU of LAI at the time point indicated (B). (C) Regardless of the inoculation dose, systemic loss of CD4⁺ T cells was observed in infected BLT humanized mice when compared to naïve animals. Shown are the percentages of human CD4⁺ T cells present in peripheral blood, lymph nodes, and spleen, as well as the percentages of CD4⁺CD8^- and CD4⁺CD8⁺ thymocytes in the human thymic organoid. The percent of CD4⁺ T cells in peripheral blood or tissues was relative to total CD3⁺ T cells while the percent of CD4⁺CD8^- and CD4⁺CD8⁺ thymocytes was relative to total thymocytes. “—” indicates naïve mice (n = 5 in PB, spleen and HTO or n = 4 in LN). Triangles indicate the increasing doses: 3000 TCIU (n = 3), 30,000 TCIU (n = 3), 600,000 TCIU (n = 3). Unpaired two-tailed t tests were performed to compare the naïve mice to the mice in each LAI infection dose group within the same tissue. If no difference was detected, the comparison is unmarked (alpha = 0.05). Comparisons yielding significant differences are represented by a line connecting the arrows above the respective bars (*p < 0.05; **p < 0.01).