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CCR 5 expression, haplotype and immune activation in protection from infection in HIV ‐exposed uninfected individuals in HIV ‐serodiscordant relationships
Author(s) -
Jaumdally Shameem Z.,
Picton Anabela,
Tiemessen Caroline T.,
Paximadis Maria,
Jaspan Heather B.,
Gamieldien Hoyam,
Masson Lindi,
Coetzee David,
Williamson AnnaLise,
Little Francesca,
Gumbi Pamela P.,
Passmore JoAnn S.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12743
Subject(s) - serodiscordant , immunology , chemokine , cytokine , cd38 , immune system , cohort , biology , haplotype , medicine , virus , genotype , viral load , gene , genetics , stem cell , antiretroviral therapy , cd34
Summary Several host factors have been implicated in resistance to HIV infection in individuals who remain HIV ‐seronegative despite exposure. In a cohort of HIV ‐serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T‐cell activation in resistance to HIV infection. Males and females in stable long‐term relationships with either HIV ‐infected or uninfected partners were recruited, blood T‐cell activation ( CD 38, HLA ‐ DR , CCR 5 and Ki67) and plasma cytokine concentrations were evaluated. The HIV ‐negative exposed individuals had significantly lower frequencies of CCR 5 + CD 4 + and CD 8 + T cells than unexposed individuals. Mean fluorescence intensity of CCR 5 expression on CD 4 + T cells was significantly lower in HIV ‐negative exposed than unexposed individuals. Protective CCR 5 haplotypes ( HHA / HHF *2, HHF *2/ HHF *2, HHC / HHF *2, HHA / HHA , HHA / HHC and HHA / HHD ) tended to be over‐represented in exposed compared with unexposed individuals (38% versus 28%, P = 0·58) whereas deleterious genotypes ( HHC / HHD , HHC / HHE , HHD / HHE , HHD / HHD and HHE / HHE ) were under‐represented (26% versus 44%; P = 0·16). Plasma concentrations of interleukin‐2 ( P = 0·02), interferon‐ γ ( P = 0·05) and granulocyte–macrophage colony‐stimulating factor ( P = 0·006) were lower in exposed compared with unexposed individuals. Activation marker expression and systemic cytokine concentrations were not influenced by gender. We conclude that the dominant signature of resistance to HIV infection in this cohort of exposed but uninfected individuals was lower T‐cell CCR 5 expression and plasma cytokine concentrations.