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Delayed differentiation of potent effector CD8(+) T cells reducing viremia and reservoir seeding in acute HIV infection.

Delayed differentiation of potent effector CD8(+) T cells reducing viremia and reservoir seeding in acute HIV infection.
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Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R, Tardif V, Cartwright P, Vandergeeten C, Bakeman W, Nichols CN, Pinyakorn S, Hansasuta P, Kroon E, Chalermchai T, O'Connell R, Kim J, Phanuphak N, Robb ML, Michael NL, Chomont N, Haddad EK, Ananworanich J, Trautmann L, ,


Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R, Tardif V, Cartwright P, Vandergeeten C, Bakeman W, Nichols CN, Pinyakorn S, Hansasuta P, Kroon E, Chalermchai T, O'Connell R, Kim J, Phanuphak N, Robb ML, Michael NL, Chomont N, Haddad EK, Ananworanich J, Trautmann L, , (click to view)

Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R, Tardif V, Cartwright P, Vandergeeten C, Bakeman W, Nichols CN, Pinyakorn S, Hansasuta P, Kroon E, Chalermchai T, O'Connell R, Kim J, Phanuphak N, Robb ML, Michael NL, Chomont N, Haddad EK, Ananworanich J, Trautmann L, ,

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Science translational medicine 9(377) pii 10.1126/scitranslmed.aag1809

Abstract

CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8(+) T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8(+) T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8(+) T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8(+) T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.

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