Blood, 15 August 2001, Vol. 98, No. 4, pp. 895-896
Mysteries of HIV pathogenesis explained
Infection and loss of CD4 helper T cells is considered an
underlying mechanism for the progressive demise of the immune system in
HIV-infected patients. But it fails to provide an adequate explanation
for certain clinical observations. For example, why do some patients
remain relatively healthy with CD4 counts of fewer than 200 while
others with similar or even higher CD4 counts succumb to Kaposi
sarcoma? New data from Liu and colleagues (page 1182) suggest that a
recently identified subpopulation of blood dendritic cell (DC) able to
produce copious amounts of type I interferon may provide some of the
answers to this conundrum. These cells are variously termed DC2s,
interferon-producing cells (IPCs), or plasmacytoid DCs. The
investigation analyzed the number of IPCs in peripheral blood of
HIV-infected patients at different stages of disease and showed a
progressive depletion with increasing plasma virus load, an observation
confirmed by our own recent studies (Donaghy et al, Blood, in press).
Furthermore, patients who were able to suppress virus growth and
remained healthy for more than 10 years were found to have elevated
numbers of IPCs compared with uninfected controls. Perhaps the most
striking finding was the correlation between low numbers of IPCs (fewer
than 2/µL was considered critical) and opportunistic infections. The
finding of Kaposi sarcoma patients with low IPC numbers but high CD4
T-cell counts was also revealing. These findings contrasted with
patients showing IPC counts higher than 2 IPCs/µL who remained
healthy despite very low CD4 T-cell numbers. The critical role of IPCs in HIV pathogenesis indicated by these studies suggests that monitoring IPC numbers may be of value and that strategies that increase the
numbers of these cells, such as treatment with flt-3 ligand, may have
therapeutic value.
Steven Patterson
Imperial College School of Medicine
