Monocyte accessory cell function in patients infected with the human immunodeficiency virus

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Previous studies indicated peripheral blood monocytes (Mo) from HIV-infected patients are poor accessory cells (AC).
• These earlier findings were limited by using autologous T cells, potentially confounding results.

Purpose of the Study:

• To re-evaluate the accessory cell function of monocytes from HIV-infected individuals using allogeneic T cells.
• To investigate the specific T cell responses affected by monocyte dysfunction in HIV infection.

Main Methods:

• Monocyte accessory cell function was assessed using Concanavalin A (Con A), pokeweed mitogen (PWM), and mixed leukocyte reaction (MLR) assays.
• Allogeneic T cells from uninfected volunteers were used as responders.
• T cell proliferation and CD4 lymphocyte viability were measured.
• Antigen-specific T cell stimulation assays were performed using mumps-specific T cell lines.

Main Results:

• Monocytes from HIV-infected patients were comparable to those from uninfected individuals in supporting Con A and PWM-stimulated lymphocyte proliferation.
• However, HIV-infected monocytes were inferior to normal monocytes in stimulating a mixed leukocyte reaction.
• This defect was not due to HIV-induced suppression or lymphocyte death.
• HIV-infected monocytes could still stimulate antigen-specific T cell lines, indicating functional MHC Class II (DR) expression.

Conclusions:

• Monocytes from HIV-infected patients retain accessory cell function for mitogen-driven and antigen-specific T cell responses.
• A significant defect exists in their ability to stimulate resting T cells in response to alloantigen or potentially new antigens.
• This monocyte dysfunction may contribute to the impaired immune responsiveness observed in individuals with HIV infection.