Dendritic cells and HIV infection; immunity with viral transmission versus compromised cellular immunity?

In this commentary we propose that changes in immune activity in HIV 1 infection are secondary to two aspects of the function of dendritic antigen presenting cells (DC). Firstly DC initiate primary proliferative and cytotoxic T cell responses to HIV but disseminate virus to T cells. Secondly, balanced against the development of protective immunity is progressive inhibition of the capacity of DC to initiate primary T cell responses. With regard to viral transmission via DC, recent studies provide direct evidence that virus has evolved in vivo by passage between DC and T cells and that DC can act as a reservoir for virus. Thus, phylogenetic trees of the sequences of V3 loops of HIV viruses in individual blood samples show evolution via DC and T cells, and plasma virus can be related preferentially to that derived from DC. In functional studies, DC from asymptomatic individuals (lacking lymphadenopathy and without treatment) cause low levels of stimulation of allogeneic lymphocytes in the mixed leukocyte reaction (MLR). By contrast, lymphocytes from these patients respond to normal allogeneic DC. Our recent evidence shows that DC stimulate an MLR by transfer of alloantigens to DC of the responder type with subsequent syngeneic stimulation of T cells. The failure of T cell stimulation by DC in HIV infection therefore shows an incapacity of these DC to transfer antigenic signals to other DC but DC that acquire and present antigen directly to stimulate T cells are still functional. The latter Situation provides encouragement that immunotherapy via DC may be feasible. However, DC from HIV infected individuals promote antibody production in B cells suggesting that the initial interaction of HIV with DC produces autocrine effects oil DC populations that promote interaction with B cells rather than with T cells. Treatment that pushes the DC back towards stimulating T cells, despite increased viral dissemination, may promote protective immunity.