HIV infection of TKO-BLT mice. (A-B) Data from mucosally and (C-F) intraperitoneally infected mice. (A) Viral load levels (HIV p24 ±standard error of the mean [SEM]) in plasma from HIV-infected mice collected at the indicated time points. Mice were challenged at 19 to 24 wpt. (B) CD4/CD8 T-cell ratios and frequency of activated CD8 T cells (CD38⁺) in mucosally challenged mice that became HIV⁺ or remained HIV⁻ 4 wpi compared with prechallenge values. Unpaired 2-tailed t tests were performed between the groups at 4 wpi. (C) Viral loads in plasma as measured by p24 ELISA (±SEM) at the indicated intervals after intraperitoneal infection with 3000 or 7000 TCIU of HIV_JR-CSF. Mice were challenged at 17 wpt. (D) Immunostaining for HIV p24 (red) and Iba1⁺ macrophages (green) in thymic organoids from representative HIV⁺ and HIV⁻ TKO-BLT mice. Magnified 20×. The images were captured from a Nikon Digital Sight DS-Ri1 camera on a Nikon Eclipse 55i with a Plan Fluor 20X/0.05 objective at 20°C with Prolong gold with 4,6 diamidino-2-phenylindole and AlexaFluor 488 and 555 using NIS Elements software. Hue on the red channel was changed from 0 to 60 to make the color visible to red/green colorblinds using ACD Canvas 14 software. (E) Significant reductions in the plasma CD4 T-cell count over 4 weeks of infection (1-way analysis of variance with Tukey post-test) and the correlation between plasma p24 level and peripheral CD4 T-cell frequency and activation (CD38⁺) at 4 wpi. (F) Positive correlations between plasma p24 levels at 4 wpi and CD8 T-cell proliferation (Ki67⁺), activation (HLA-DR⁺), and expansion of the T_em subset. ***P < .001; **P < .01.