Bone Marrow–derived Dendritic Cells, Infection With Human Immunodeficiency Virus, and Immunopathology

Abstract

Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may become productive as they mature. The distribution of DC within genital mucosa and their susceptibility to infection particularly with clade E viruses could be reflected in the ease of heterosexual transmission. Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protective immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infected DC and T cells. In asymptomatic infection, fewer dendritic cells with reduced capacity to stimulate CD4 T cell proliferation are found before evidence of T cell abnormalities, and these early changes in antigen-presenting cells may result in a decline in the production of CD4 memory T cells. However, DC fuel ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus underlie two major features of early HIV infection--loss in CD4+ memory T cells and persistence of antibody production. In AIDS, infected dendritic and epithelial cells within the thymus may affect maturation and contribute to loss of the "naive" T cell population. Further loss of memory T cells may occur through syncytium formation with infected DC. Finally, in AIDS patients, there is a failure in the development and the function of DC from CD34+ stem cells. In conclusion, the infection of dendritic cells, loss in their numbers, and changed signaling to T cells may shape the pattern of immunity during infection with HIV-1. Conversely, treatments that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

“…As the co-stimulatory molecule CD80 is essential for the induction of potent immune responses (Harris & Ronchese, 1999), infected cells fail to stimulate T cells in mixed leukocyte reactions (Jenne et al, 2000(Jenne et al, , 2001. Other well-known examples of viruses causing defects in APCs are measles virus (Fugier-Vivier et al, 1997) and HIV (Knight & Patterson, 1997).…”

“…In order to escape immune responses, gene products of many viruses interfere with DC function (Kobelt et al, 2003). Wellknown examples of viruses causing defects in DC maturation or function include HSV-1 (Kruse et al, 2000;Mikloska et al, 2001;Mossman et al, 2001;Samady et al, 2003), measles virus (Fugier-Vivier et al, 1997), vaccinia virus (Engelmayer et al, 1999;Jenne et al, 2001) and human immunodeficiency virus (HIV) (Knight & Patterson, 1997).…”

Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells

“…Dendritic cells (DCs) are the most potent APCs in the initiation of an immune response and adaptive immunity, and may be one of the earliest cell types exposed to pathogens (7)(8)(9). Expression of large numbers of different cytokines and costimulatory factors provides DCs with an ability to induce primary anti-tumor immune responses (9,10).…”

“…Expression of large numbers of different cytokines and costimulatory factors provides DCs with an ability to induce primary anti-tumor immune responses (9,10).…”

Phenotypic and functional modulation of porcine monocyte-derived dendritic cells for foot-and-mouth disease virus

“…The active induction of immune suppression is one mechanism by which viruses escape clearance (Rouse et al, 1986). Several viruses are known to target dendritic cells (DCs) and impair antiviral T cell responses (Knight et al, 1997;Fugier-Vivier et al, 1997;Andrews et al, 2001;Sevilla et al, 2000;Kruse et al, 2000;Ho et al, 2001).…”