FIG 1.

SIV-specific CD8⁺ T cells can migrate throughout B cell follicles, including germinal centers (GCs). (A) Representative lymph node section stained with Mamu-A1*001/Gag CM9 tetramers to label SIV-specific CD8⁺ T cells (red; indicated with arrows in the enlargement), with IgM antibodies (blue) to define follicles (F), and with Ki67 antibodies (green) to label the GC. Confocal images were collected with a 20× objective. Bar, 100 μm. (B) Frequencies of tetramer⁺ SIV-specific CD8⁺ T cells in different compartments of the lymph nodes and spleen during chronic SIV infection. Data for samples from the spleen are indicated in red, whereas all other data are for lymph nodes. There were no significant differences between frequencies of tetramer⁺ SIV-specific CD8⁺ T cells in GC and non-GC follicular areas (P = 0.85). Frequencies of extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells were 109% (95% confidence interval [CI], 60 to 172%) higher than the frequencies of tetramer⁺ SIV-specific CD8⁺ T cells in the GC (P < 0.0001) and 104% (95% CI, 56 to 166%) higher than those in the non-GC follicular areas (P < 0.0001). (C) Relationship between frequencies of follicular and extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells. The frequency of extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells predicted the frequency of follicular tetramer⁺ SIV-specific CD8⁺ T cells. For every 1-log₁₀ increase in extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, there was an estimated 1.14-log₁₀ (95% CI, 0.86- to 1.42-log) increase in the frequency of follicular tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.0001). After adjusting for extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, tissue type (lymph node or spleen) was not a significant predictor of follicular tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.39). (D) Relationship between frequencies of GC and extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells. The frequency of extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells predicted the frequency of GC tetramer⁺ SIV-specific CD8⁺ T cells. For every 1-log₁₀ increase in extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, there was an estimated 1.11-log₁₀ (95% CI, 0.34- to 1.88-log) increase in the frequency of GC tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.014). After adjusting for extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, tissue type (lymph node or spleen) was not a significant predictor of GC tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.96). (E) Relationship between frequencies of non-GC follicular and extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells. The frequency of extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells predicted the frequency of non-GC follicular tetramer⁺ SIV-specific CD8⁺ T cells. For every 1-log₁₀ increase in extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, there was an estimated 0.87-log₁₀ (95% CI, 0.45- to 1.28-log) increase in the frequency of non-GC follicular tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.0030). After adjusting for extrafollicular tetramer⁺ SIV-specific CD8⁺ T cells, tissue type (lymph node or spleen) was not a significant predictor of non-GC follicular tetramer⁺ SIV-specific CD8⁺ T cells (P = 0.86).