Changing roles of CD3⁺CD8^low T cells in combating HIV-1 infection

Background:Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8(low)) or high levels (CD8(high)) on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for >= 2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3(+)CD8(low) T cells and their counterpart CD3(+)CD8(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors, CD3(+)CD8(low) T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3(+)CD8(low) T cells gradually decreased. Simultaneously, CD3(+)CD8(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3(+)CD8(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38(-)HLA-DR(+)CD8(low) T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load (r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count (r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3(+)CD8(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3(+)CD8(low) T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3(+)CD8(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI (r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3(+)CD8(low) T cells, but comparable amounts of CD3(+)CD8(high) T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3(+)CD8(low) T cells than CD3(+)CD8(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3(+)CD8(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3(+)CD8(low) T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3(+)CD8(high) T cells.