Altered cytokine expression in T lymphocytes from human immunodeficiency virus Tat transgenic mice

Abstract

Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for this type of strategy. Transgenic mice can be used to investigate the in vivo effects of Tat on the developing and dynamic immune system and on cellular gene expression. Thus, we have generated transgenic mice that harbor the HIV type 1 Tat gene under the transcriptional control of the human CD2 gene regulatory elements. This expression cassette results in high-level, tissue-specific transcription of the transgene within the T-cell compartment. In this report, we demonstrate the effects of Tat on the in vivo immune system. CD2-Tat transgenic mice show no signs of aberrant thymic development and have normal levels of T-cell subsets in the thymus and peripheral lymphoid organs. However, activated T cells from transgenic mice contain increased levels of tumor necrosis factor beta mRNA as well as biologically active tumor necrosis factor protein and express elevated levels of transforming growth factor ␤ and interleukin-4 receptor mRNA. These increased cytokine levels do not appear to alter mitogen-or antigen-stimulated responses or induce the formation of dermal lesions in ageing mice. Such investigations should provide insight into the combination of host immune factors mediating pathogenesis in HIV infection.

Human immunodeficiency virus type 1 Tat protein induces an intracellular calcium increase in human monocytes that requires DHP receptors: involvement in TNF-alpha production

“…A variety of functions have been associated with HIV-1 Tat protein, including induction of apoptosis (Westendorp et al, 1995b), immunosuppressions (Badou et al, 2000;Shearer and Clerici, 1993), stimulation or inhibition of cytokine production (Brady et al, 1995;Nath et al, 1999; 6. Functional DHP receptors on primary human monocytes.…”

Murine Models of Chronic Viral Infections and Associated Cancers

“…HIV-1 undistinguishable from the parental virus was isolated from the spleen, lymph nodes, and the skin of the affected mice (five out of five) [ 59 ]. Transgenic mice that carry individual HIV-1 genes, e.g., tat , were also constructed [ 61 , 62 ]. Like other models, mice transgenic for individual viral genes lacked both receptors necessary for viral infection and cofactors necessary for efficient viral replication and were tolerant to production of the viral proteins.…”

Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses

“…In line with HBV and HCVtg mice, several attempts have been made to generate HIVtg mice resulting in substantial understanding of virus-host interactions and clinical manifestation of acquired immune deficiency syndrome (AIDS) symptoms or the development of Kaposi's sarcoma [32][33][34][35][36]. However, HIVtg mice showed discrepancies in tissue-and immunopathology (reviewed in [37]).…”