2B4+ CD8+ T cells play an inhibitory role against constrained HIV epitopes

Abstract

Cytotoxic T cells play a critical role in the control of HIV and the progression of infected individuals to AIDS. 2B4 (CD244) is a member of the SLAM family of receptors that regulate lymphocyte development and function. The expression of 2B4 on CD8 + T cells was shown to increase during AIDS disease progression. However, the functional role of 2B4 + CD8 + T cells against HIV infection is not known. Here, we have examined the functional role of 2B4 + CD8 + T cells during and after stimulation with HLA B14 or B27 restricted HIV epitopes. Interestingly, IFN-γ secretion and cytotoxic activity of 2B4 + CD8 + T cells stimulated with HIV peptides were significantly decreased when compared to influenza peptide stimulated 2B4 + CD8 + T cells. The expression of the signaling adaptor molecule SAP was downregulated in 2B4 + CD8 + T cells upon HIV peptide stimulation. These results suggest that 2B4 + CD8 + T cells play an inhibitory role against constrained HIV epitopes underlying the inability to control the virus during disease progression.

Evolving role of 2B4/CD244 in T and NK cell responses during virus infection

“…High level expression of 2B4 and other inhibitory receptors has also been observed on exhausted CD8 T cells specific for LCMV (Wherry et al, 2007), HIV (Aldy et al, 2011), HCV (Bengsch et al, 2010), and HBV (Raziorrouh et al, 2010). Blockade of 2B4–CD48 interactions restored murine LCMV- (Blackburn et al, 2009) and human HBV-specific (Raziorrouh et al, 2010) CD8 T cell effector functions during in vitro culture.…”

T cell exhaustion during persistent viral infections

“…2B4 is upregulated on activated T cells during many infections including HIV, HBV, CMV, EBV, and LCMV (Aldy et al, 2011; Blackburn et al, 2008b; Peritt et al, 1999; Raziorrouh et al, 2010; Schlaphoff et al, 2011) and has both positive and negative effects which depend upon its levels of expression (Chlewicki et al, 2008). Crosslinking 2B4 in conjunction with TCR activation of either bulk or HCV-specific CD8 T cells increased the proliferation of 2B4 lo but not 2B4 hi subsets (Schlaphoff et al, 2011).…”

Lymphocyte Activation Gene-3 Expression Defines a Discrete Subset of HIV-Specific CD8+T Cells That Is Associated with Lower Viral Load

“…31 Expression of 2B4 on CD8 + T cells has been associated with HIV disease progression and decreased killing activity. 32,33 However, recent studies on HIV-specific CD8 + T cell exhaustion has been shown to be associated with the complex expression of PD-1, CTLA-4, and 2B4 but not LAG-3. 16 We found no evidence of PD-1, CTLA-4, or 2B4 coexpression on CD8…”