Cytotoxic-T-Cell Responses, Viral Load, and Disease Progression in Early Human Immunodeficiency Virus Type 1 Infection

Abstract

In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.

Long-Term Maintenance of gp120-Specific Immune Responses by Genetic Vaccination with the HIV-1 Envelope Genes Linked to the Gene Encoding Flt-3 Ligand

“…The poor immunogenicity of HIV envelope protein gp120 could be partly due to its inherent biological properties (71,72,73). Covalent attachment of FLex to gp120 could have converted gp120 to a better immunogen for induction of robust immune responses in mice.…”

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

“…The pelleted RNA was resuspended in diethyl-pyrocarbonate-treated water and the poly (A) 1 portion of total RNA, was converted into cDNA using 2´5 mm oligo(dT) (Perkin Elmer, Norwalk, CT, USA) and 2´5 units MULV reverse transcriptase (Perkin Elmer). The sequences of 24 TCRBV subfamilies specific primers (BV 1, 2, 3, 4, 5´1, 5´3, 6´1, 6´2, 7,8,9,11,12,13,14,15,16,17,18,20,21,22,23,24) and of a TCR constant b-chain (BC) primer used in this study were previously described by Maslanka et al [20]. Amplications of target cDNA were performed as reported by Gorochov et al [5].…”

“…The decreased diversity of the CD4 1 T cell receptor (TCR) repertoire, arizing from HIV-1-induced deletion of CD4 1 T cell clones, has been also invoked as responsible for loss of antigen specific responsiveness [10]. In addition, anti-HIV cytotoxic activity, that plays a fundamental role in limiting virus spread during the early phases of infection, generally decreases with time, in association with disease progression [11]. Finally, chemokine receptors, in addition to regulate the HIV entry into the target cells, could also contribute to AIDS immunopathogenesis [12].…”

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6 Pol and p6 Gag Late Domain Associated with Drug Resistance

“…HIV-1-specific cytolytic activities were determined after stimulation with peptides in a chromium release assay (32). Briefly, cryopreserved PBMC were thawed and cultured overnight at 37°C under 5% CO 2 .…”

“…Most often, this occurs by substitution of an amino acid at a position in the epitope critical for interaction with its cognate MHC or T-cell receptor, but it can also involve changes in flanking residues (11,46). The known epitopes may differ in their abilities to stimulate highly avid CTL among HIV-positive individuals, gain immunodominance, and acquire escape mutations (11,14,22,24,32,47). The properties of the epitopes that account for these differences merit further understanding, since they potentially govern viral selection and replication fitness within the host and among populations at risk.…”