Immunoregulatory cytokine changes result from HIV infection, with decreased type 1 cytokines that enhance cellular immunity (CI) and increased type 2 cytokines that augment humoral immunity (HI). IL-12 and IL-10 enhance CI and HI, respectively, and are produced by monocytes/macrophages (M/M), important targets of HIV infection. M/M from HIV+ patients produced reduced levels of IL-12 and increased levels of IL-10, as did M/M infected in vitro with HIV. IL-12 p40 and p35 mRNA expression was reduced in advanced but not in asymptomatic patients. Therapeutic trials of pediatric AIDS patients with HIV protease inhibitors suggested that patients who presented with reduced viral loads and increased CD4 counts exhibited a trend toward normalized IL-12 and IL-10 production. Immunization of AIDS patients with an influenza vaccine did not result in detectable changes in viral load, CD4 count or apoptotic T cell death. Patients with CD4 counts >300/ul exhibited temporary increases in flu-specific T cell responses, whereas patients with lower CD4 counts showed no improved T cell responses to flu. Seronegative, HIV-exposed, T cell-responsive individuals exhibited a dominant type 1 cytokine profile when stimulated with HIV antigens, whereas HIV-infected individuals showed a dominant type 2 cytokine pattern. CD8+ T cell lines resulting from HLA alloantigen mixed lymphocyte stimulation generated a factor that blocked HIV infection of PHA stimulated autologous and allogeneic targets, and also inhibited CMV infection of human fibroblast target cell lines. This alloantigen-stimulated CD8 anti-viral factor does not appear to be RANTES, MIP-1a or MIP-1b. Thus, this allostimulated factor is capable in vitro of blocking both HIV and one of the opportunistic viruses that is problematic in AIDS patients. T cell lines generated from patients with Wiskott-Aldrich Syndrome (WAS) were found to be defective in their ability to load peptide antigens in association with HLA class I at 37oC. A similar defect was not found for peptide loading with HLA class II. This class I-associated defect was """"""""corrected"""""""" by lower temperature (28oC) or by excess b2-microglobulin, or by introduction of the WASP gene. Three different phenotypic patterns were detected among the patients' cell lines: those that exhibited no defect at either temperature; those that were corrected at 28oC; those that were not corrected at 28oC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009267-14
Application #
2463767
Study Section
Special Emphasis Panel (EIB)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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