Functional deficiencies in two distinct interferon alpha-producing cell populations in peripheral blood mononuclear cells from human immunodeficiency virus seropositive patients.

Two populations of IFN-alpha producing cells (IPC) were examined to determine whether they are coordinately dysregulated in human immunodeficiency virus (HIV) disease. IFN-alpha produced in response to herpes simplex virus (HSV) and Sendai virus (SV) was measured and the frequencies of the IPC were obtained by ELISpot assay. IPC that respond to HSV (natural IFN-alpha producing cells) and those responding to SV (predominantly monocytes) were present, on average, at 7.6 and 138 per 10(4) PBMC in healthy controls, respectively. More patients had a reduced IFN-alpha response to HSV than to SV, and individual patients did not show a decreased response to SV without a decreased response to HSV. Neither IPC function was correlated with CD4+ cell levels. We conclude that the defects in IFN-alpha production in these two cell populations arise independently, possibly due to differences in susceptibility to HIV infection or molecular regulation.

Viral induction of low frequency interferon-alpha producing cells.

The human peripheral blood mononuclear cells responsible for IFN-alpha production in response to viral stimuli have been most often described as either monocytes (as typified by the response to Sendai virus) or as a light density, HLA-DR+ population which is negative for most cell surface markers characteristic of mature T cells, B cells, monocytes, or natural killer cells (as typified by the response to Herpes simplex virus (HSV)). The frequency of IFN-alpha-producing cells (IPC) responding to Sendai virus is typically 10-fold or more higher than those responding to HSV. In the current study, we have used ELISpot assays to determine the frequency of IPC responding to DNA and RNA viruses including HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus (NDV) and human immunodeficiency virus (HIV). The enveloped viruses but not the nonenveloped viruses (adenovirus and SV40) elicited an IFN-alpha response. The frequency of IPC for each of the other viruses was more similar to the low frequency HSV-responding population than to the higher frequency Sendai virus response. These included several viruses in the same family as Sendai virus, namely the paramyxo viruses measles, mumps, and NDV. IPC were also tested for sensitivity to the lysosomotropic drug chloroquine, which diminishes IFN-alpha produced in response to HSV but not Sendai virus. With the exception of Sendai virus, chloroquine treatment abrogated the majority of IFN-alpha produced and IPC against each of the viruses. We conclude that low frequency, nonmonocytic NIPC account for the majority of IFN-alpha production in response to different viruses.

Decreased frequency of functional natural interferon-producing cells in peripheral blood of patients with the acquired immune deficiency syndrome.

Deficient in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) occurs in patients infected with the human immunodeficiency virus (HIV), with the most deficient responses associated with opportunistic infections (OI). The peripheral blood mononuclear cells (PBMC) which produce IFN-alpha in response to HSV are light density, HLA-DR+ cells lacking any unique surface markers and have been termed "natural interferon-producing cells" (NIPC). In this study, IFN-alpha responses were measured and the ELISpot assay was utilized to determine the frequency of NIPC in response to HSV. As expected, HIV-infected patients had depressed IFN-alpha production. In the ELISpot assay, healthy controls had a mean frequency of 1:703 NIPC among PBMC; each NIPC made approximately 2 international units (IU) of IFN-alpha. HIV-infected patients on average had fourfold less NIPC than controls and produced 1 IU IFN-alpha/NIPC; the plaque size for patient samples was often smaller than that for controls. NIPC frequency and IFN-alpha production were lowest in patients with a history of OI. In conclusion, deficient IFN-alpha production by AIDS patients results from reductions in both the frequency and the activity of NIPC, probably reflecting a gradual turning off of IFN-alpha production.

Immunosuppression in men with bowenoid papulosis.

The immune status of four men with bowenoid papulosis was evaluated. Each case had been refractory to multiple methods of treatment. Three of the men had other infections and demonstrated a depletion of T4-helper cells. Two of these patients were anergic on skin testing, and the third showed weak reactivity. The fourth patient, who had no evidence of additional infections, had a normal T4 value and T4/T8 ratio, but was anergic on skin testing. All the men were serologically negative for human immunodeficiency virus antibodies. One of the immunosuppressed patients developed squamous cell carcinoma of the tongue, which, along with his bowenoid papulosis, contained human papillomavirus 16 DNA. We suggest that patients with persistent bowenoid papulosis be investigated for altered immune status and followed up as potential candidates for the development of epithelial malignant neoplasms.