Interleukin 12-Augmented T Cell Proliferation of Peripheral Blood Mononuclear Cells from HIV-Seropositive Individuals Is Associated with Interleukin 12 Receptor β2 Upregulation
| Autor: | Rebekah L. Puls, Qi Rong Huang, Matthew L. Jones, Elizabeth M. Benson, Carolyn A. Webber, Judy Young |
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| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_treatment
T cell Immunology HIV Infections Biology Lymphocyte Activation Peripheral blood mononuclear cell Downregulation and upregulation HIV Seronegativity Virology HIV Seropositivity medicine Humans RNA Messenger Cell growth Receptors Interleukin-12 Receptors Interleukin biology.organism_classification Interleukin-12 Recombinant Proteins Up-Regulation Infectious Diseases Cytokine medicine.anatomical_structure Lentivirus Interleukin-12 receptor HIV-1 Leukocytes Mononuclear Interleukin 12 |
| Zdroj: | AIDS Research and Human Retroviruses. 19:283-292 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/088922203764969483 |
| Popis: | Interleukin 12 (IL-12) production is believed to be impaired in individuals with HIV infection and this impairment manifests early in disease, when the CD4(+) cell counts are within normal values. The reduced antigen-specific and mitogen-stimulated T cell-proliferative responses that occur in HIV infection can be corrected by the addition of recombinant human interleukin 12 (rhIL-12). As the IL-12 receptor (IL-12R) is central to the IL-12 signaling pathway, we examined whether the augmentation of antigen-specific proliferation of HIV(+) peripheral blood mononuclear cells (PBMCs) related to altered IL-12R expression. rhIL-12 augmented antigen-specific proliferation of HIV(+) PBMCs but not of HIV(-) PBMCs. Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell surface as detected by flow cytometry. However, examination of mRNA showed that both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs when compared with HIV(-) PBMCs. After mitogen activation there was an increase in IL-12R beta 1 expression on the cell surface of HIV(+) and HIV(-) PBMCs and this level was not altered by coculture with rhIL-12 or interferon gamma (IFN-gamma). However, coculture of phytohemagglutinin (PHA)-activated HIV(+) or HIV(-) PBMCs with rhIL-12 (but not IFN-gamma) increased IL-12R beta 2 expression on the cell surface of both populations. Examination at the message level showed a correction of IL-12R beta 1 to normal levels with activation that was further enhanced by rhIL-12 coculture for both the HIV(+) and HIV(-) PBMCs. However, although the level of IL-12R beta 2 for the HIV(+) PBMCs was normalized by PHA, rhIL-12 caused a further augmentation. This information provides a strong link between IL-12R upregulation, and the significant improvement in antigen-specific HIV-proliferative responses seen with the addition of rhIL-12. It also reveals that the dysfunction in IL-12R expression seen in cells from HIV(+) patients occurs at the transcriptional level. In addition, we provide further evidence that IL-12R beta 1 and IL-12R beta 2 regulation in human PBMCs is independent of IFN-gamma. |
| Databáze: | OpenAIRE |
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