Abstract
Although CD8+ T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1 infection is not as well understood. Impaired HIV-specific CD8+ T cell responses may underlie the persistently high viral loads observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8+ T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT. The frequency (0.088–3.9% of CD3+CD8+ cells) and phenotype (CD27+CD28−, CD45RA+/−, CD57+/−, HLA-DR+, CD95+) of infant HIV-specific CD8+ T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23–24 months post-infection a high frequency of HIV-specific CD8+ T cells expressed HLA-DR (mean 80%, range 68–85%) and CD95 (mean 88%, range 79–96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIV-specific CD8+ T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.
Highlights
The natural history of human immunodeficiency virus type-1 (HIV-1) infection in infants differs markedly from adults
7 infants had responses directed at HIV-1 epitopes for which we were able to construct tetramers and had sufficient cells cryopreserved for flow cytometry studies
Persistent activation and expression of CD95 on HIVspecific CD8+ T cells may result in the apoptotic elimination of virus-specific T cells, further enabling the persistence of viral replication, and perhaps explaining the poor prognosis of HIV-1 infected infants
Summary
The natural history of human immunodeficiency virus type-1 (HIV-1) infection in infants differs markedly from adults. Plasma viral load peaks during acute infection and is subsequently reduced to a .1 log lower level set-point over the 6–8 weeks [1]. This viral load set-point may be maintained for years, sometimes at levels below detection. Infants experience very high plasma viral loads (often more than 1 million copies/ml) and lack the characteristic decline to set-point observed in adults [2,3,4,5,6]. In the absence of antiretroviral therapy (ART), 2-year mortality rates as high as 52% have been reported in African cohorts [7,8,9,10]
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