HIV infection generates dysfunctional CD8^low SP CD8 thymocytes in the SCID-hu Thy/Liv mouse model. Saline, or 1000 50% tissue culture infective dose (TCID₅₀) of X4-tropic (NL4-3), R5-tropic (Ba-L), or dual-tropic X4-R5 (primary isolate JD) HIV were inoculated into individual cohorts of 30-40 SCID-hu Thy/Liv mice each. In most cohorts, several groups were also treated with antiretroviral drugs (eg, 3TC). Viral load (HIV RNA content per million total cells) as well as phenotypic and functional parameters were measured by flow cytometry in human thymocytes from each implant 3 to 7 weeks after inoculation. (A) FACS plot of SP8 thymocytes in Mock- and HIV-infected human thymus. (B) Correlation between CD8α expression in SP8 thymocytes and MHC-I expression in double-positive (DP) thymocytes from individuals within the same cohort of HLA-A2⁺ SCID-hu Thy/Liv mice, including animals inoculated with medium (Mock), HIV NL4-3, Ba-L, or JD, and compared with IFNα treatment alone. (C-E) Calcium flux response after TCR/CD8 cross-linking in SP8 thymocytes from a cohort of SCID-hu Thy/Liv mice, 21 days postinoculation with NL4-3: representative calcium flux kinetic from 2 mock-infected (blue line) or 2 NL4-3-infected mice (red line). (C) Calcium flux peak responses in all animals (D) and correlation with CD8α expression in SP8 thymocytes (E). P values were calculated using the Mann-Whitney test for group analysis and by Spearman rank correlation for correlation test. R² from the Pearson coefficient of correlation is also indicated.