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Moreover, HIV-specific CD4+ T cells from lungs were present at significantly higher frequencies and manifested a significantly more polyfunctional response (~?15%) compared with HIV-specific CD4+ T cells from blood (XL184 chemical structure expanded blood and cervical T-cell responses to Gag showed that the magnitude of responses largely correlated significantly between compartments. Studies investigating the relationship between the magnitude or breadth of HIV-specific cytotoxic T lymphocytes in blood and HIV clinical status have reported conflicting findings.[30-32, see more 36, 37] Few studies have evaluated the relationship between the frequency or functionality of HIV-specific T-cell responses at mucosal surfaces and HIV clinical status. A significant inverse relationship was observed between plasma viral load and CD8+ T cells expressing CD107a in fresh blood, expanded blood and expanded cervical lines. This indicates that the ability of CD8+ T cells from both the cervix and in blood to degranulate was highest in women with lowest plasma viral load. It is likely that polyfunctional responses systemically as well as at mucosal surfaces are a consequence of an intact immune system in individuals with low viral replication, rather than the cause of low virus replication. The finding that cervical and systemic CD107a responses are similarly effected by clinical status is not surprising given our finding that (i) blood CD107a responses are significantly associated with cervical CD107a responses; (ii) plasma viral load is strongly associated with JQ1 genital tract HIV shedding (either as the result of passive transudate from plasma across mucosal surfaces or through active homing of HIV-infected target cells to the mucosa in individuals with high systemic viral loads), and (iii) CD4 counts between compartments are also linked. Gumbi et?al.[16] showed that IFN-��+ T-cell responses to HIV Gag were also not associated with protection from HIV genital shedding. Similarly, we show here by measuring four functions of cervical Gag-specific CD8+ T cells that these cells are not able to protect against genital HIV shedding.