KIR3DL1-Negative CD8 T Cells and KIR3DL1-Negative Natural Killer Cells Contribute to the Advantageous Control of Early Human Immunodeficiency Virus Type 1 Infection in HLA-B Bw4 Homozygous Individuals

Abstract

Bw4 homozygosity in human leukocyte antigen class B alleles has been associated with a delayed acquired immunodeficiency syndrome (AIDS) development and better control of human immunodeficiency virus type 1 (HIV-1) viral load (VL) than Bw6 homozygosity. Efficient CD8 T cell and natural killer (NK) cell functions have been described to restrain HIV-1 replication. However, the role of KIR3DL1 expression on these cells was not assessed in Bw4-homozygous participants infected with HIV-1 CRF01_A/E subtype, currently the most prevalent subtype in China. Here, we found that the frequency of KIR3DL1-expressing CD8 T cells of individuals homozygous for Bw6 [1.53% (0-4.56%)] was associated with a higher VL set point (Spearman r_s = 0.59, P = 0.019), but this frequency of KIR3DL1⁺CD8⁺ T cells [1.37% (0.04-6.14%)] was inversely correlated with CD4 T-cell count in individuals homozygous for Bw4 (r_s = -0.59, P = 0.011). Moreover, CD69 and Ki67 were more frequently expressed in KIR3DL1^-CD8⁺ T cells in individuals homozygous for Bw4 than Bw6 (P = 0.046 for CD69; P = 0.044 for Ki67), although these molecules were less frequently expressed in KIR3DL1⁺CD8⁺ T cells than in KIR3DL1^-CD8⁺ T cells in both groups (all P < 0.05). KIR3DL1^-CD8⁺ T cells have stronger p24-specific CD8⁺ T-cell responses secreting IFN-γ and CD107a than KIR3DL1⁺CD8⁺ T cells in both groups (all P < 0.05). Thus, KIR3DL1 expression on CD8 T cells were associated with the loss of multiple functions. Interestingly, CD69⁺NK cells lacking KIR3DL1 expression were inversely correlated with HIV-1 VL set point in Bw4-homozygous individuals (r_s = -0.52, P = 0.035). Therefore, KIR3DL1^-CD8⁺ T cells with strong early activation and proliferation may, together with KIR3DL1^-CD69⁺NK cells, play a protective role during acute/early HIV infection in individuals homozygous for Bw4. These findings highlight the superior functions of KIR3DL1^-CD8⁺ T cells and KIR3DL1^-CD69⁺NK cells being a potential factor contributing to delayed disease progression in the early stages of HIV-1 infection.

Keywords: Bw4 homozygotes; KIR3DL1 receptor; acute/early infection; human immunodeficiency virus type 1; immunity.