Properties of HTLV-I transformed CD8+ T-cells in response to HIV-1 infection.

HIV-1 infection studies of primary CD8(+) T-cells are hampered by difficulty in obtaining a significant number of targets for infection and low levels of productive infection. Further, there exists a paucity of CD8-expressing T-cell lines to address questions pertaining to the study of CD8(+) T-cells in the context of HIV-1 infection. In this study, a set of CD8(+) T-cell clones were originated through HTLV-I transformation in vitro, and the properties of these cells were examined. The clones were susceptible to T-cell tropic strains of the virus and exhibited HIV-1 production 20-fold greater than primary CD4(+) T-cells. Productive infection resulted in a decrease in expression of CD8 and CXCR4 molecules on the surface of the CD8(+) T-cell clones and antibodies to these molecules abrogated viral binding and replication. These transformed cells provide an important tool in the study of CD8(+) T-cells and may provide important insights into the mechanism(s) behind HIV-1 induced CD8(+) T-cell dysfunction.

Modulation of HIV-1 transcription by cytokines and chemokines.

Infection with HIV results in the modulation of circulating levels of many host factors. Several host proteins that are up-regulated in HIV infection have the potential to influence virus replication. More specifically, the transcription of HIV-1 can be modulated in vivo by host proteins, including cytokines and chemokines. Cytokines modulate transcription mediated by the HIV-1 long terminal repeat (LTR) via multiple signal transduction pathways with resulting recruitment of numerous transcription factors, including NFkappaB, C/EBP, AP-1, TCF-1alpha, NF-IL-6 and ISGF-3. The effects on transcription may vary depending upon the cell type studied and upon the timing of the exposure of infected or transfected cells to cytokines. Furthermore, studies of cytokine mediated activation or inhibition of LTR mediated transcription may also be affected by the presence of the HIV-1 trans-activating protein, Tat, which has significant impact upon the redox state of the cell. This review will examine the complexities of the positive and negative control of HIV transcription by cytokines and chemokines.

The role of CD8+ T cell soluble factors in human immunodeficiency virus infection.

Cell-mediated immune responses are important for the control of HIV replication in vivo. Cytotoxic CD8+ T cells (CTL) recognize and kill HIV-infected cells which display MHC class-I proteins. In addition to the recognition and killing of infected cells, CD8+T cells can interfere with stages of the HIV life-cycle. Chemokines produced by CD8+ T cells bind to their seven-transmembrane G protein-coupled receptors resulting in a block in the entry of HIV into macrophages and T cells. In addition, activated CD8+ T cells produce factors which strongly modulate HIV at the level of transcription. This review will focus primarily on the current knowledge of the multifactorial functions of CD8+ T cells in HIV infection. An understanding of the mechanisms involved in the CD8-mediated control of transcription may identify other factors with potential value in the treatment of HIV infection.