Figure 4. HIV-Specific CD8⁺ T Cells Are Poorly Cytolytic and Express Low Levels of T-Bet and CXCR5 in LNs.

(A) Flow plots (left) showing FLGKIWPSHK (FK10)/HLA-A*0201 and ILKEPVHGV (IV9)/HLA-A*0201 tetramer stains of PBMCs and LNMCs from the same subject, and frequency of matched HIV-tetramer⁺ CD8⁺ T cell responses (right) in PBMCs and LNMCs.

(B) Compartmentalization of HIV-tetramer⁺ CD8⁺ T cell responses within different memory subsets: central memory (CM; CCR7⁺ CD27⁺ CD45RO⁺), transitional memory (TM; CCR7⁻ CD27⁺ CD45RO⁺), effector memory (EM; CCR7⁻ CD27⁻ CD45RO⁺), and terminally differentiated (TD; CCR7⁻ CD27⁻ CD45RO⁻).

(C) Flow cytometry plots (left) showing gzmB expression in HIV-tetramer⁺ CD8⁺ T cells in PBMCs and LNMCs from the same subject, and frequency of perforin and gzmB expression for all HIV-tetramer⁺ CD8⁺ T cells (right) in PBMCs and LNMCs.

(D) Frequency of perforin and gzmB co-expression in matched HIV-tetramer⁺ CD8⁺ T cells (left) in PBMCs (blue) and LNMCs (red), and correlation between perforin⁺ and gzmB⁺ HIV-tetramer⁺ CD8⁺ T cells (right) in PBMCs (blue) and LNMCs (red).

(E) Frequency of perforin⁺ HIV-tetramer⁺ CD8⁺ T cells within the T-bet^higheomes^dim population (left) in PBMCs (blue) and LNMCs (red), and correlation between perforin⁺ and HIV-tetramer⁺ CD8⁺ T cells (right) in PBMCs (blue) and LNMCs (red).

(F) Flow plots (left) showing HIV-tetramer⁺ CD8⁺ T cell expression of CXCR5 and perforin for two distinct specificities in LNMCs from the same subject, frequency of CXCR5⁺ versus CXCR5⁻ HIV-tetramer⁺ CD8⁺T cells (middle) in LNMCs, and perforin expression in CXCR5⁺ and CXCR5⁻ HIV-tetramer⁺ CD8⁺ T cells (right) in LNMCs. Flow plots are representative of chronically infected HIV⁺ individuals. Statistical significance within a subject group between tissue compartments was determined using the Mann-Whitney two-tailed test. Statistical significance for correlations was determined using Spearman’s test. Ranges shown on plots represent median and interquartile range (IQR).