Protective genotypes in HIV infection reflect superior function of KIR3DS1+ over KIR3DL1+ CD8+ T cells.

Certain human class I histocompatibility-linked leukocyte antigen (HLA)/killer cell immunoglobulin-like receptor (KIR) genotypic combinations confer more favourable prognoses upon exposure to human immunodeficiency virus (HIV). These combinations influence natural killer (NK) cell function, thereby implicating NK cells in protection from HIV infection or disease progression. Because CD8(+) T cells restrict HIV replication, depend upon HLA class I antigen presentation and can also express KIR molecules, we investigated how these HLA/KIR combinations relate to the phenotype and function of CD8(+) T cells from uninfected controls and individuals with chronic HIV infection.

Positioning of APOBEC3G/F mutational hotspots in the human immunodeficiency virus genome favors reduced recognition by CD8+ T cells.

Due to constitutive expression in cells targeted by human immunodeficiency virus (HIV), and immediate mode of viral restriction upon HIV entry into the host cell, APOBEC3G (A3G) and APOBEC3F (A3F) have been considered primarily as agents of innate immunity. Recent bioinformatic and mouse model studies hint at the possibility that mutation of the HIV genome by these enzymes may also affect adaptive immunity but whether this occurs in HIV-infected individuals has not been examined. We evaluated whether APOBEC-mediated mutations within common HIV CD8+ T cell epitopes can potentially enhance or diminish activation of HIV-specific CD8+ T cells from infected individuals.

Heteroclitic peptides enhance human immunodeficiency virus-specific CD8(+) T cell responses.

The inability of human immunodeficiency virus (HIV)-specific CD8(+) T cells to durably control HIV replication due to HIV escape mutations and CD8(+) T cell dysfunction is a key factor in disease progression. A few HIV-infected individuals termed elite controllers (EC) maintain polyfunctional HIV-specific CD8(+) T cells, minimal HIV replication and normal CD4(+) T lymphocyte numbers. Thus, therapeutic intervention to sustain or restore CD8(+) T cell responses similar to those persisting in EC could relieve terminal dependence on antiretrovirals.

Nociceptin induces hypophagia in the perifornical and lateral hypothalamic area.

Nociceptin/orphanin FQ (N/OFQ) is known to induce food intake when administered into the lateral ventricle or certain brain areas. This is somewhat contradictory to its reward-suppressing role, as food is a strong rewarding stimulus. This discrepancy may be due to the functional diversity of N/OFQ's target brain areas.

Killer cell immunoglobulin-like receptor 3DL1 licenses CD16-mediated effector functions of natural killer cells.

Activating receptor-mediated recognition of stress-induced ligands or IgG antibody bridging of tumor or pathogen-associated antigens to the FcγRIII CD16 triggers NK cells to kill transformed and infected cells with reduced HLA-I expression. According to the licensing hypothesis, NK cells become competent for activating receptor-mediated triggering after a formative encounter between a NK inhibitory receptor and its ligand. This general hypothesis is supported by murine and human studies, but to date, evidence of a role for such licensing in human ADCC is ambiguous.

Human immunodeficiency virus type I-specific CD8+ T cell subset abnormalities in chronic infection persist through effective antiretroviral therapy.

Background: Effective highly active antiretroviral therapy (HAART) reduces human immunodeficiency virus (HIV) replication, restores CD4+ T lymphocyte counts and greatly reduces the incidence of opportunistic infections. While this demonstrates improved generalized immune function, rapid rebound to pre-treatment viral replication levels following treatment interruption indicates little improvement in immune control of HIV replication. The extent to which HAART can normalize HIV-specific CD8+ T cell function over time in individuals with chronic infection remains an important unresolved issue.

Distinct phenotype of unrestricted cytotoxic T lymphocytes from human immunodeficiency virus-infected individuals.

Introduction: Human immunodeficiency virus (HIV)-infected individuals have CD8(+) cytotoxic T lymphocytes (CTL) that kill activated uninfected T lymphocytes. These CTL are independent of class Ia human histocompatibility-linked leukocyte antigens (HLA-Ia).

Methods: To further characterize these CTL, we investigated their possible restriction to non-classical class Ib HLA-E molecules and their expression of natural killer cell receptors (NKR) that are often affected in HIV infection.

Association of TNF-alpha polymorphisms in Crohn disease.

Clinical and molecular studies implicate tumor necrosis factor alpha (TNF-alpha) as a key mediator in the initiation and propagation of Crohn disease (CD). Genetic associations have been documented between promoter polymorphisms of TNF-alpha and CD; however, these associations have not been universally replicated. In this study, we set out to examine the association of five promoter TNF-alpha polymorphisms in CD subjects from a founder population.

Association of SEEK1 polymorphisms in Crohn's disease.

Crohn's disease (CD) is an inflammatory bowel disease that is likely the result of an interplay of genetic and environmental factors. Recent studies have postulated similarities in genetic susceptibility of CD and psoriasis. Because the +39604 SEEK1 polymorphism in chromosome 6p has recently been associated with psoriasis, the prevalence of this polymorphism, as well as two additional single nucleotide polymorphisms in the SEEK1 gene, in patients with CD from the Newfoundland population were determined.