Naive CD8^low T cells from untreated HIV-infected subjects are impaired with respect to calcium flux response and phosphorylation of p38MAPK after TCR stimulation. Calcium flux and the level of phosphorylation of p38MAPK were measured by flow cytometry in naive (CD45RA^highCD27^high) CD8⁺ T cells from PBMCs of study A (described in Figure 1B). Calcium flux was measured after TCR/CD8 cross-linking, and phosphorylation of p38MAPK was measured by the fold induction of p38MAPK phosphorylation from PHA-stimulated compared with mock-stimulated samples (see “Phenotypic and functional analysis in HIV-infected subject PBMCs” and supplemental Methods and Schweneker et al²⁰ ). (A-C) Calcium flux responses over time were determined by the percentage of responding naive CD8⁺ T cells over 75% of the baseline level (prior TCR stimulation). Calcium flux responses are shown in 3 HAART and 3 Prog. CD4 < 350 (A) and for all subjects (B), and were correlated with the fold-induction of phopho-p38MAPK (C left) and shown in a representative example (C right). (D-E) Finally, both calcium flux (D) and phospho-p38MAPK (E) responses were correlated with the CD8α expression in naive (CD45RA^highCD27^high) CD8⁺ T cells. P values are indicated for Spearman rank correlation test. R² is also indicated (from the Pearson coefficient of correlation).