HIV-specific CD8+ lymphocytes in semen are not associated with reduced HIV shedding.
Sexual contact with HIV-infected semen is a major driving force behind the global HIV pandemic. Little is known regarding the immune correlates of virus shedding in this compartment, although HIV-1-specific CD8+ T cells are present in semen. We collected blood and semen from 27 chronically HIV-infected, therapy-naive men without common sexually transmitted infections or urethral inflammation and measured HIV-1 RNA viral load and cytokine/chemokine levels in both compartments. HIV-1 RNA levels were 10-fold higher in blood than semen, but discordantly high semen shedding was associated with higher semen levels of the proinflammatory cytokines IL-6, IL-8, IL-12, and IFN-gamma. Virus-specific CD8+ T cell epitopes were mapped in blood by IFN-gamma ELISPOT, using an overlapping HIV-1 clade B peptide matrix, and blood and semen CD8+ T cell responses were then assayed ex vivo using intracellular IFN-gamma staining. HIV-specific CD8+ responses were detected in 70% of semen samples, and their frequency was similar to or higher than blood. There was no correlation between the presence of virus-specific CD8+ T cells in semen and levels of HIV-1 RNA shedding. Among participants with detectable CD8+ IFN-gamma semen responses, their relative frequency was not associated with reduced HIV-1 RNA shedding, and their absolute number was correlated with higher levels of HIV-1 RNA semen shedding (r = 0.6; p = 0.03) and of several proinflammatory cytokines. Neither the presence nor the frequency of semen HIV-specific CD8+ T cell IFN-gamma responses in semen correlated with reduced levels of HIV RNA in semen.
Sheth
Prameet M
PM
Department of Medicine, University of Toronto, Ontario, Canada.
Danesh
Ali
A
Shahabi
Kamnoosh
K
Rebbapragada
Anuradha
A
Kovacs
Colin
C
Dimayuga
Rowena
R
Halpenny
Roberta
R
Macdonald
Kelly S
KS
Mazzulli
Tony
T
Kelvin
David
D
Ostrowski
Mario
M
Kaul
Rupert
R
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D012661:Semen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D017201:Virus Shedding / Q000276:immunology*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012367:RNA, Viral; D007371:Interferon-gamma; D007781:Lactoferrin