Antigen presentation by macrophages but not by dendritric cells in human immunodeficiency virus (HIV) infection.

Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (Mø) are only effective in stimulating memory responses.¹, ² Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked.³ Here comparisons between DC and Mø in stimulating secondary T-cell responses in HIV infection were made. Adherent Mø, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [³H]thymidine in 20 μ1 hanging drop cultures. DC, but not Mø, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, Mø from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not Mø function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells^4–6 may be cumulative; failure of secondary activation (e.g. by Mø) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches. [ABSTRACT FROM AUTHOR]