In studies aimed at defining monocyte and macrophage function in patients with human immunodeficiency virus (HIV) infection, we found impaired in vivo Fc receptor-specific clearance in 20 of 25 patients with acquired immunodeficiency syndrome (AIDS) and in five of 13 patients with AIDS-related illnesses. The in vivo function of macrophage C3 receptors was also found to be abnormal: AIDS patients had a relatively large release of cells back into the circulation, suggesting failure of macrophage phagocytosis. The antibody-dependent cell-mediated cytotoxicity of circulating mononuclear cells was significantly lower in AIDS patients than in healthy controls. Monocyte nonspecific phagocytosis and surface marker expression were intact. Defective monocyte and macrophage function is an integral part of the immunopathology of AIDS, leading to the failure to control opportunistic pathogens. Whether these defects are due to intrinsic infection of the mononuclear phagocytes with HIV or are secondary to other events in the network of HIV infection remains to be determined.

https://www.jstor.org/stable/info/4454672

Role of the Mononuclear Phagocyte System in the Immunopathogenesis of Human Immunodeficiency Virus Infection and the Acquired Immunodeficiency Syndrome

Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions.

Initially described as an antiviral cytokine, IFN-α has been subsequently shown to affect several cellular functions, including cellular differentiation and proliferation. For these reasons, IFN-α is currently used in clinical practice for the treatment of viral infections and malignancies. In this manuscript, we show two novel mechanisms concomitantly responsible for the antiproliferative effect of IFN-α. First, long-term treatment with IFN-α of primary CD4 + T cells reduced surface expression of CD3 and CD28. These events resulted in decreased phosphorylation of the mitogen-activated extracellular signal-regulated activating kinase and its substrate extracellular signal-regulated kinase, leading to diminished production of IL-2. Second, IFN-α treatment of primary CD4 + T cells reduced proliferative response to stimulation in the presence of exogenous IL-2 by markedly decreasing mRNA synthesis and surface expression of CD25 (α-chain), a critical component of the IL-2R complex. These results may be relevant for the antitumor effects of IFN-α and may help us to better understand its detrimental role in the inhibition of proliferation of the bulk of CD4 + T cells (uninfected cells) in HIV-infected persons, who are known to overproduce IFN-α.

IFN-α2b Reduces IL-2 Production and IL-2 Receptor Function in Primary CD4+ T Cells

Impaired in-vitro proliferation of hemopoietic precursors in HIV-1-infected subjects.

HIV-1 infection in vitro of normal bone marrow mononuclear cells (BMMC) depleted of mature T cells was studied. BMMC depleted of either CD3, CD2, or both could replicate HIV-1 irrespective of the presence of macrophages/monocytes. Infected bone marrow cells were shown to differentiate during the culture into CD3+, CD4+, CD8+, and CD1+ cells, whereas noninfected BMMC gave rise to CD3+, CD4+, and CD8+ cells. Moreover, 9-14% of the cells also expressed the viral proteins p24 and gp120 on their surface. Double staining studies revealed that 72 and 83% of the CD4+ cells expressed the gp120 and p24, respectively, suggesting that virus replication occurred in CD4+ cells. T cell colony growth from infected BMMC, either unfractionated or depleted of mature T cells, was impaired in a time-dependent manner, and the differentiation capacity of T cell precursors was abnormal. Colony cells displayed an immature cell phenotype (CD1+ cells) and the viral proteins gp120 and/or p24 could also be detected on CD1+ cells. In addition, pooled colony cells derived from infected CD2- and CD3-depleted BMMC could infect normal mitogen-activated lymphocytes in coculture experiments. These findings strongly suggest that HIV-1 can infect immature bone marrow T cells and be transmitted to the progeny, but the massive viral replication occurs only when the cells differentiate toward CD4+ cells.

/pdf/replication-of-the-human-immunodeficiency-virus-1-and-qxuhymf0d1.pdf

Replication of the human immunodeficiency virus 1 and impaired differentiation of T cells after in vitro infection of bone marrow immature T cells.

Peripheral blood adherent cells from AIDS patients inhibit normal T-colony growth through decreased expression of interleukin 2-receptors and production of interleukin 2.

Daniel Vittecoq

Papers

Peripheral blood adherent cells from AIDS patients inhibit normal T-colony growth through decreased expression of interleukin 2-receptors and production of interleukin 2.