Microanatomic Relationships Between CD8+ Cells and HIV-1-Producing Cells in Human Lymphoid Tissue in Vivo

Abstract

Host immune responses are unable to fully suppress HIV-1 replication in lymphoid tissues. Microanatomic relationships between HIV-1-producing cells and CD8+ cells in lymphoid tissues were analyzed to determine whether there was evidence for an immune privileged site or impaired recognition of virus-producing cells. CD8+ cell phenotypes were determined on disaggregated inguinal lymph node cells by flow cytometry for seven untreated HIV-1-infected subjects. Microanatomic relationships between HIV-1-producing cells and CD8+ cells were analyzed in lymph node sections from 15 HIV-1-infected individuals using in situ hybridization and immunohistochemical staining. Most (median, 96%) lymph node CD8+ cells coexpressed CD3. Frequencies of virus-producing cells detected by in situ hybridization correlated with plasma HIV-1 RNA concentration (Spearman rho = 0.70; p =.02; n = 11). The percentage of lymph node cells adjacent to virus-producing cells that were CD8+ (median, 29%) was not statistically different from the percentage of CD8+ cells in lymphoid tissue overall (median, 34%; p =.09). Multiple explanations could account for the observation that CD8+ cells do not preferentially accumulate around virus-producing cells including the possibility that HIV-1-specific CD8+ cells cannot recognize virus-producing cells. Further studies are necessary to determine whether HIV-1-specific CD8+ T cells aggregate around virus-producing cells in lymphoid tissue.