Abstract
In recent years, the prevalence of HIV-1 infection has been rapidly increasing among men who have sex with men (MSM). However, it remains unknown how the host immune system responds to the infection in this population. We assessed the quantity of HIV-specific CD8+ T-cell responses by using Elispot assay and their functionalities by measuring 5 CD8+ T-cell evaluations (IL-2, MIP-1β, CD107a, TNF-α, IFN-γ) with flow cytometry assays among 18 primarily and 37 early chronically HIV-infected MSM. Our results demonstrated that subjects at early chronic phase developed HIV-specific CD8+ T-cell responses with higher magnitudes and more diversified functionalities in comparison with those at primary infection. However, populations with IL-2+ CD107a+ or in combination with other functionality failed to develop in parallel. The multifunctional but not monofunctional HIV-specific CD8+ T cells were associated with higher CD4+ T -cell counts and lower viral loads. These data revealed that prolonged infection from primary to early chronic infection could selectively increase the functionalities of HIV-specific CD8+ T cells in HIV-infected MSM population, the failure to develop IL-2 and cytotoxic functionalities in parallel may explain why the increased HIV-specific CD8+ T cells were unable to enhance the containment of HIV-1 replication at the early chronic stage.
Highlights
The HIV-specific CD8+ T-cell responses play an important role in controlling viremia following initial HIV-1 infection, which is supported by several important observations and correlative studies
The response breadth as defined by the number of peptide pools able to raise positive HIV-specific CD8+ T cells was significantly higher in early chronic infection group than the primary infection group, suggesting that the prolonged HIV-infection could stimulate the host immune system to recognize new antigenic peptide pools and thereby broaden the HIV-specific CD8+ T-cell responses. These data were further supported by the observation that the overall responding frequency to 17 peptide pools in early chronic infection group was significantly higher than that in primary infection group (Fig.1b), a dramatic increase in recognition was unambiguously observed for peptide pools of Pol2, Pol4, Pol5, Env3, Env5 and Tat and Rev peptides (Tat+Rev); Interestingly, only slight increase was observed for the most frequently recognized pools of Gag2, Env2 and Nef with the responding frequencies at 92.7%, 87.3% and 90.9%, respectively, indicating epitopes in those pools are highly immunogenic and able to mount efficient recognition at the primary infection phase (Fig. 1b)
We examined and compared HIV-specific CD8+Tcell functional hierarchy between HIV-1 primarily infected (,6 months) and early chronically infected men who have sex with men (MSM) subjects (12-36 months) by using peptide derived from consensus B clade
Summary
The HIV-specific CD8+ T-cell responses play an important role in controlling viremia following initial HIV-1 infection, which is supported by several important observations and correlative studies. Strong correlations were observed between HLA heterogeneity and survival advantage and between certain HLA class I alleles and non-progressive HIV infection [6], for example, HIV-specific CD8+T-cell responses restricted by HLA-B*57 were typically associated with a non-progressive clinical consequence or at least a slower disease progression [7,8]. Though cumulative evidences demonstrated a crucial role for antiviral effects of CD8+ T cells, most HIV infected individuals experience progressive loss of CD4+ T cells and fail to control plasma viremia despite the presence of vigorous HIV-specific CD8+ T-cell responses. A study using the most comprehensive approaches has shown that the magnitude of HIV-specific CD8+
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