Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in the number of CD8(+) and CD4(+) cells as well as the CD4(+) chemoattractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood while increasing extracellular...

Soluble MHC class I molecules loaded with antigenic peptides are available either to detect and to enumerate or, alternatively, to sort and expand MHC class I-restricted and peptide-reactive T cells. A defined number of MHC class I/peptide complexes can now be implemented to measure T cell responses induced upon Ag-specific stimulation, including CD3/CD8/zeta-chain down-regulation, pattern, and...

CD8(+) and CD8(-) T cell lines expressing the same antigen-specific receptor [the 2C T cell receptor (TCR)] were compared for ability to bind soluble peptide-MHC and to lyse target cells. The 2C TCR on CD8(-) cells bound a syngeneic MHC (K(b+))-peptide complex 10-100 times less well than the same TCR on CD8(+) cells, and the CD8(-) 2C cells lysed target cells presenting this complex very poorly...

Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on...

Human immunodeficiency syndrome (HIV) infection leads to a progressive loss of T-cell-mediated immunity associated with T-cell apoptosis. We report here that CD4’ and CD8’ T cells from HIV-l-infected persons are sensitive to Fas (CD95/APO-l)-mediated death induced either by an agonistic anti-Fas antibody or by the physiologic soluble Fas ligand, although showing no sensitivity to tumor necrosi...

IL-7 signaling is essential for optimal CD8 T cell function, homeostasis and establishment of memory. We have previously shown decreased expression of the IL-7 receptor alpha-chain (CD127) on CD8 T cells from HIV-infected patients with active viral replication. We have also shown that soluble HIV Tat protein specifically down-regulates CD127 on the surface of CD8 T cells and impairs cell prolif...

Vβ5(+) regulatory T cells (Tregs), which are specific for a mouse endogenous retroviral superantigen, become activated and proliferate in response to Friend virus (FV) infection. We previously reported that FV-induced expansion of this Treg subset was dependent on CD8(+) T cells and TNF-α, but independent of IL-2. We now show that the inflammatory milieu associated with FV infection is not nece...

Topical antigen application is a focus of current vaccine research. This immunization route mimics natural antigen exposure across a barrier tissue and generates T cells imprinted for skin-selective homing. Soluble antigens introduced through this route require cross-presentation by DC to generate CD8 T cell responses. Here we have explored the relative contribution of various skin-derived DC s...

During reinfection, high-affinity IgG Abs form complexes with both soluble Ag and Ag displayed on the surface of infected cells. These interactions regulate cellular activation of both innate cells and B cells, which express specific combinations of activating FcγRs (FcγRI, FcγRIII, FcγRIV) and/or the inhibitory FcγR (FcγRIIB). Direct proof for functional expression of FcγR by Ag-specific CD8 T...

Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint pathways involved in regulation of the immune responses and suppression of anti-tumor defense. PD-1/B7-H1-blocking antibodies improve immune responses such as cytotoxic activity of CD8+/CD4+T cells and also increase mortality of tumor cells; however their use is accompanied by adverse effects in pat...