Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication
J. Clin. Invest. David A. Garber, et al. 113:836 doi:10.1172/JCI19442 [
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Figure 2CS blockade attenuates the generation and in vivo CTL activity of SIV-specific CD8
+ T cell responses. (A) Levels of Gag
181–189-specific (CTPYDINQM-specific) CD8
+ T cells (red trace), Tat
28–35-specific (STPESANL-specific) CD8
+ T cells (yellow trace), or the sum of Gag
181–189- and Tat
28–35-specific CD8
+ T cells (blue trace) as percentages of CD8
+ T cells in peripheral blood (left axes) and the level of the sum of Gag
181–189- and Tat
28–35-specific CD8
+ T cells as a percentage of CD8
+Ki67
+ T cells (black trace) in peripheral blood (right axes). Left column, control macaques; right column, CS blockade macaques. Gray bars denote the treatment period. (B) Levels (%) of peripheral blood CD8
+ T cells that exhibit the Ki67 antigen, a marker of cellular proliferation, by flow cytometry. Control macaques: ROz5 (black), RBm6 (blue), RVy5 (red), RYt5 (green). CS blockade macaques: REp6 (black), REo6 (blue), RIc6 (red), RCr5 (green). The gray bar denotes the treatment period. (C) Nucleotide sequences of cDNA clones encoding SIV
tat exon 1 were determined at the indicated times after infection and were compared to the WT parental SIVmac239 sequence. Frequencies of cDNA clones that exhibited one or more nonsynonymous mutations within the region encoding the Tat
28–35 (STPESANL) epitope are shown for individual macaques in the control or CS blockade groups. (D) Correlation of the level of Tat
28–35-specific (STPESANL-specific) CD8
+ T cells and the frequency of mutation within the Tat
28–35 coding region at 20 days following SIV infection. The
P value was determined by the Spearman rank correlation test. Control macaques (circles): ROz5 (black), RBm6 (blue), RVy5 (red), RYt5 (green); CS blockade macaques (triangles): REp6 (black), REo6 (blue), RIc6 (red), RCr5 (green).