Presence of distinct subsets of cytolytic CD8+ T cells in chronic HIV infection.

Cytolytic T lymphocytes (CTL) play an important role in the control of HIV infection. The eventual failure to contain HIV-1 infection may arise because of a functional impairment of HIV-specific CTL. We evaluated Gag-specific cytotoxicity in HIV-1-positive Ugandans.

CD4 T cell activation as a predictor for treatment failure in Ugandans with Plasmodium falciparum malaria.

Host immunity plays an important role in response to antimalarial therapy but is poorly understood. To test whether T cell activation is a risk factor for antimalarial treatment failure, we studied CD4(+) and CD8(+) T cell activation in 31 human immunodeficiency virus-negative Ugandan patients 5-37 years of age who were treated for uncomplicated Plasmodium falciparum malaria. Increased CD4(+) T cell activation, as indicated by co-expression of HLA-DR and CD38, was an independent risk factor for treatment failure (hazard ratio = 2.

Depletion of regulatory T cells in HIV infection is associated with immune activation.

Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate CD4(+) T cell depletion. Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses. We asked whether loss of Tregs during HIV infection mediates immune activation in a cross-sectional study of 81 HIV-positive Ugandan volunteers.

Human immunodeficiency virus-specific responses in adult Ugandans: patterns of cross-clade recognition.

Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections.

T cell activation in HIV-seropositive Ugandans: differential associations with viral load, CD4+ T cell depletion, and coinfection.

Immune activation is thought to play a major role in the pathogenesis of human immunodeficiency virus (HIV). This effect may be particularly relevant in Africa, where endemic coinfections may contribute to disease progression, perhaps as a consequence of enhanced immune activation. We investigated the expression of CD38 and human leukocyte antigen (HLA)-DR on T cells in 168 HIV-seropositive volunteers in Uganda.

Cooperative roles of CTLA-4 and regulatory T cells in tolerance to an islet cell antigen.

Adoptive transfer of ovalbumin (OVA)-specific T cells from the DO.11 TCR transgenic mouse on a Rag(-/-) background into mice expressing OVA in pancreatic islet cells induces acute insulitis and diabetes only if endogenous lymphocytes, including regulatory T cells, are removed. When wild-type OVA-specific/Rag(-/-) T cells, which are all CD25(-), are transferred into islet antigen-expressing mice, peripheral immunization with OVA in adjuvant is needed to induce diabetes.

Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo.

The failure of CD25+ regulatory T cells (Tregs) to proliferate after T cell receptor (TCR) stimulation in vitro has lead to their classification as naturally anergic. Here we use Tregs expressing a transgenic TCR to show that despite anergy in vitro, Tregs proliferate in response to immunization in vivo. Tregs also proliferate and accumulate locally in response to transgenically expressed tissue antigen whereas their CD25- counterparts are depleted at such sites.