Increase in dendritic cell numbers, their function and the proportion uninfected during AZT therapy

Abstract

SUMMARYThe effects of AZT treatment on the numbers, level of infection and function of peripheral blood dendritic cells (DC) were examined in patients with HIV infection. This was a cross-sectional study of patients before AZT treatment and up to 20 months after initiation of treatment. Numbers of DC separated by density gradients were below the normal range in patients before treatment, but increased between 3 and 12 months of treatment. The numbers of DC per provirus copy rose from around 100 cells to 5000 cells and this decrease in viral load in DC was significant between 3 and 20 months of treatment. The capacity of DC to stimulate allogeneic T cell proliferation was low before treatment and significantly higher between 6 and 12 months after the start of AZT. This study indicated that AZT treatment produced beneficial effects on DC by increasing their numbers, reducing the provirus load and increasing their function in stimulating T cells. These results support the thesis that the function of these potent antigen-presenting cells is important in development of immunological defects in AIDS, and that effects of AZT treatment on DC may provide a measure of its therapeutic effect.

Dendritic and Natural Killer Cell Subsets Associated with Stable or Declining CD4+Cell Counts in Treated HIV‐1–Infected Children

“…We analyzed the percentage of Lin-1 Ϫ /HLA-DR + / CD11c + myeloid DCs, to determine how HIV infection affects this DC subset in HIV-infected viremic and suppressed children. Contrary to previous observations by our group and others in adults [7,9,10,41], no significant difference was observed among uninfected age-matched control (median 0.20% [IQR, 0.14%]), suppressed (median, 0.17% [IQR, 0.16%]), and viremic (median, 0.21% [IQR, 0.21%]) children, which suggests that myeloid DCs in children might be less affected by viral replication than those in adults. However, the percentage of myeloid DCs was significantly lower ( ) in viremic chil-P !…”

Persistent Decreases in Blood Plasmacytoid Dendritic Cell Number and Function Despite Effective Highly Active Antiretroviral Therapy and Increased Blood Myeloid Dendritic Cells in HIV-Infected Individuals

“…activity (22), and more recently a moderate increase in PDC after HAART (19 To analyze the potential alteration in DC function in circulating blood during HIV infection, we evaluated phenotypic and biological properties of two major subsets of DC from a cross-sectional cohort of HIV-infected donors and uninfected control subjects. Our data show that MDC number is inversely associated with viral load in untreated chronic HIV-1-infected patients and increases under HAART, in contrast to a sustained loss of PDC (CD123 ϩ or BDCA-2 ϩ ) subset and a concurrent decrease in IFN-␣ secretion.…”

Dendritic Cells in Innate Immune Responses Against HIV

“…In the peripheral blood, DCs are mostly immature. In humans they comprise two major populations, called myeloid and plasmacytoid DCs, each corresponding approximately to half of the total DCs [3][4][5][6][7].…”

“…Because T cell responses are crucial for long-term HIV replication control, and DCs are essential in inducing primary immune responses, the hypothesis of antigen presentation defects by DCs was raised [7,72,73]. Indeed, a defect in alloantigen presentation by Langerhans cells from infected patients compared to those of their non-infected identical twin was found, whereas no defect in memory responses to specific T cell epitopes was evidenced [74] : this indicates a defect in primary, rather memory T cell response induction.…”