Immunological function of Langerhans cells in HIV infection

Langerhans cells (LCs) are one of the initial target cells for HIV following sexual exposure and they are productively infected by HIV. HIV-infected LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4⁺ T cells, leading to the dissemination of HIV. In contrast with the role of LCs in initial HIV acquisition, little is known about the modulation of immune responses by HIV-infected LCs.

We aimed to elucidate the induction of HIV-specific CD8⁺ T cells and regulatory T cells (Tregs), both of which play important roles in regulating the progression of HIV infection.

We examined the inducibility of HLA-A*0201 restricted HIV-specific CD8⁺ T cells and Tregs by HIV-primed LCs or HIV-primed dendritic cells (DCs) as a control.

The number of HIV-specific CD8⁺ T cells induced by HIV-primed monocyte-derived LCs (mLCs) was significantly higher than that by HIV-primed monocyte-derived DCs (mDCs). Additionally, HIV-specific CD8⁺ T cells induced by HIV-primed mLCs produced more IFN-γ than HIV-nonspecific CD8⁺ T cells. HIV-primed human epidermal LCs also induced IFN-γ-producing HIV-specific CD8⁺ T cells. As for the induction of Tregs, HIV-primed mLCs and human epidermal LCs significantly impaired the induction of FoxP3^hiCD45RA^- effector Tregs than HIV-unprimed mLCs and human epidermal LCs.

HIV-primed LCs trigger beneficial immune responses against HIV infection through the increased induction of HIV-specific CD8⁺ T cells and the decreased induction of effector Tregs in the initial phase of HIV infection, thereby contributing to the prolonged onset of AIDS.