Proximity of Cytomegalovirus-Specific CD8 T Cells to Replicative Senescence in Human Immunodeficiency Virus-Infected Individuals.

Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies.

Greater frequency of CD5-negative CD8(+) T cells against human immunodeficiency virus type 1 than other viruses is consistent with adaptation to antigenic variation.

Background: The CD5 protein antagonizes phosphorylation events downstream of T cell receptor (TCR) engagement to decrease T cell responsiveness. CD5-negative T cell clones respond preferentially over their CD5(+) counterparts against cells with low human histocompatibility-linked leukocyte antigen (HLA) levels. In human immunodeficiency virus type 1 (HIV-1) infection, CD5(-)CD8(+) T cells increase in prevalence with disease progression.

Hepatitis C virus-infected cells downregulate NKp30 and inhibit ex vivo NK cell functions.

Hepatitis C virus (HCV) successfully evades the immune system and establishes chronic infection in ∼80% of cases. Immune evasion may involve modulating NK cell functions. Therefore, we developed a short-term assay to assess immediate effects of HCV-infected cells on ex vivo NK cytotoxicity and cytokine production.

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.

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.