scholarly journals Phase 1 Trial of a Single Dose of Recombinant Human Interleukin–12 in Human Immunodeficiency Virus–Infected Patients with 100–500 CD4 Cells/μL

2000 ◽  
Vol 182 (4) ◽  
pp. 1070-1076 ◽  
Author(s):  
Mark A. Jacobson ◽  
David Hardy ◽  
Elizabeth Connick ◽  
Jessica Watson ◽  
Michael DeBruin
1987 ◽  
Vol 165 (4) ◽  
pp. 1230-1235 ◽  
Author(s):  
I Funke ◽  
A Hahn ◽  
E P Rieber ◽  
E Weiss ◽  
G Riethmüller

The expression of the CD4 antigen in normal human brain was investigated in parallel by immunohistochemical and Northern blot analyses. With anti-CD4 antibodies detecting different epitopes of the molecule, CD4+ neurons were defined in the cerebellum, thalamus, and pons. CD4+ glial cells were identified in the thalamus and pons. CD4-specific mRNA was detected in all three subareas and in the hippocampus, while other subareas were negative. The CD4+ cells were negative with anti-T cell antibodies (anti-CD2 and anti-CD8), as well as with antimonocyte antibodies (M-M 522 and M-M 42).


Blood ◽  
1999 ◽  
Vol 94 (3) ◽  
pp. 1003-1011 ◽  
Author(s):  
Jason D. Marshall ◽  
Jihed Chehimi ◽  
Giorgia Gri ◽  
Jay R. Kostman ◽  
Luis J. Montaner ◽  
...  

Interleukin-12 (IL-12) is a potentially critical factor in the immune response against human immunodeficiency virus (HIV) because it is important for regulating proliferation and interferon-γ (IFN-γ) production by T cells and natural killer (NK) cells, antigen presentation and accessory cell function by macrophages and dendritic cells, and cytolytic activities of cytotoxic T-lymphocyte cells and NK cells, which are all functions known to be dysfunctional in patients with acquired immune deficiency syndrome. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients have been previously shown to be deficient in the ability to produce IL-12 in response to the bacterial pathogen Staphylococcus aureus Cowan. In this study, impaired IL-12 production in cells from PBMC of HIV-infected patients compared with healthy donors was observed across a broad panel of stimuli derived from infectious pathogens with or without priming with cytokines such as IFN-γ and IL-4, which amplify the IL-12 induction signal. Analysis of p40 and p35 mRNA accumulation showed that reductions in both subunits contribute to the lower IL-12 secretion of cells from HIV-infected individuals. PBMC from HIV-infected donors also failed to upregulate the IL-12 receptor β2 chain (IL-12Rβ2) in response to mitogenic stimuli. The expression of the IL-12Rβ2 gene could, however, be restored by in vitro exposure to rIL-12. Thus, it is possible that a primary IL-12 defect may lead to secondary deficiencies in expression of the genes for IL-12Rβ2 and IFN-γ, thus amplifying immune deficiency during HIV infection.


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