Regeneration and Tolerance Factor Prevents Bystander T-Cell Death Associated with Human Immunodeficiency Virus Infection
AUTOR(ES)
Derks, Richard A.
FONTE
American Society for Microbiology
RESUMO
Human immunodeficiency virus (HIV) infection is characterized by a depletion of T cells. This depletion is caused both by the virus-induced death of infected T cells and by the death of uninfected cells (bystander depletion) by a mechanism which is largely uncharacterized. Regeneration and tolerance factor (RTF) is a subunit of the vacuolar ATPase and a protein that is involved with activation and apoptosis. Anti-RTF antibodies mediate apoptosis in T lymphocytes. When anti-RTF was added to lymphocytes from an HIV-positive individual, they underwent larger amounts of apoptosis than cells taken from healthy controls. When lymphocytes were examined by Western blotting, those from HIV-positive individuals exhibited increased levels of expression of the 50-kDa protein (P < 0.001). A 70-kDa protein was the predominant form of RTF in uninfected control lymphocytes, being expressed in 100% of individuals studied. The expression of the 50-kDa protein in HIV-positive individuals correlated with decreased absolute CD4 counts with a sensitivity of 92% and a positive predictive value of 86%. When uninfected lymphocytes were stimulated with anti-CD3 and anti-CD28, no RTF was detected during early stimulation but a 50-kDa protein was expressed during late stimulation. When the susceptibilities of the lymphocytes to anti-RTF-induced apoptosis were measured, they correlated with the size of the RTF protein expressed. The cells were not susceptible to apoptosis when the 70-kDa RTF was present but were susceptible when the 50-kDa RTF was present. We propose that the increase in the levels of the 50-kDa RTF on cells from HIV-positive individuals is important in preventing the cell from undergoing apoptosis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=515283Documentos Relacionados
- Regeneration and Tolerance Factor: a Correlate of Human Immunodeficiency Virus-Associated T-Cell Activation
- Infection of rabbit T-cell and macrophage lines with human immunodeficiency virus.
- High level of surface CD4 prevents stable human immunodeficiency virus infection of T-cell transfectants.
- Chronic polyradiculoneuropathy associated with human T-cell lymphotropic virus type I infection.
- Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.