Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.
Korey R DemersGeorge MakedonasMarcus BuggertMichael A EllerSarah J RatcliffeNilu GoonetillekeChris K LiLeigh Anne EllerKathleen RonoLucas MagangaSorachai NitayaphanHannah KibuukaJean-Pierre RoutyMark K SlifkaBarton F HaynesAndrew J McMichaelNicole F BernardMerlin L RobbMichael R BettsPublished in: PLoS pathogens (2016)
The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- hiv testing
- hepatitis c virus
- men who have sex with men
- poor prognosis
- transcription factor
- multiple sclerosis
- regulatory t cells
- south africa
- immune response
- climate change
- oxidative stress
- type iii
- binding protein
- working memory
- single molecule
- drug induced
- artificial intelligence