Abstract
BackgroundHIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate.Methodology/Principal FindingsIn this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups.Conclusions/SignificanceTogether, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.
Highlights
Host factors have a strong influence on the HIV-1-specific CD8+ T cell response and the consequent level of control exerted upon viral replication
The groups were overall well distributed with regards to age, sex and race the SS group had a slightly higher percentage of females and the no immune suppression (NS) group a slightly higher percentage of African Americans
Several studies have suggested that qualitative characteristics of the HIV-1-specific CD8+ T cell response are associated with viral control and disease progression [2,26,27,28,29,30]
Summary
Host factors have a strong influence on the HIV-1-specific CD8+ T cell response and the consequent level of control exerted upon viral replication. Individuals who are homozygous at any of the three HLA class I loci have a more rapid progression to AIDS, compared to those who are heterozygous at these alleles [1] suggesting an advantage to having a diverse repertoire of HIV-1-specific CD8+ T cell responses [2,3,4,5,6,7]. HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate
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