Activation of CD8(+) T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis

T cell activation through the T cell receptor is necessary to achieve a specific and effective immune response. We report here that stimulation of CD8(+) T cells through the T cell receptor complex leads to de novo expression of the CD4 antigen on the cell surface that results in susceptibility of CD8(+) T cells to HIV infection. In addition, activation of peripheral blood mononuclear cells from HIV-infected individuals results in the appearance of double-positive CD4(+)/CD8(+) T cells, which become infected by endogenous HIV. HIV DNA sequences could be detected in uncultured and sorted mature CD3(+)CD8(+) T cells from HIV(+) individuals. These results suggest a new mechanism by which HIV could attack the immune system and may help to explain the CD8(+) T cell defects in AIDS patients

Unsung hero Robert C. Gallo

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Unsung Hero Robert C. Gallo

Awarding the Nobel prize in physiology or medicine to Francoise Barré-Sinoussi and Luc Montagnier for the discovery of HIV-1, the causative agent of AIDS, is timely given the harm that the virus continues to inflict on the people of the world. While these awardees fully deserve the award, it is equally important to recognize the contributions of Robert C. Gallo. Gallo definitively proved HIV-1 as the cause of AIDS through the successful isolation and long-term cultivation of HIV-1 and developed a diagnostic kit that prevented new infections and saved thousands of lives. These contributions, together with Gallo's earlier discovery of interleukin-2 (fundamental for growing HIV-1 in vitro) and of HTLV-1, the first human pathogenic retrovirus, warrant equal recognition

Investigating the role of mitochondria in type 2 diabetes lessons from lipidomics and proteomics studies of skeletal muscle and liver.

Mitochondrial dysfunction is discussed as a key player in the pathogenesis of type 2 diabetes mellitus (T2Dm), a highly prevalent disease rapidly developing as one of the greatest global health challenges of this century. Data however about the involvement of mitochondria, central hubs in bioenergetic processes, in the disease development are still controversial. Lipid and protein homeostasis are under intense discussion to be crucial for proper mitochondrial function. Consequently proteomics and lipidomics analyses might help to understand how molecular changes in mitochondria translate to alterations in energy transduction as observed in the healthy and metabolic diseases such as T2Dm and other related disorders. Mitochondrial lipids integrated in a tool covering proteomic and functional analyses were up to now rarely investigated, although mitochondria]. lipids might provide a possible lynchpin in the understanding of type 2 diabetes development and thereby prevention. In this chapter state-of-the-art analytical strategies, pre -analytical aspects, potential pitfalls as well as current proteomics and lipidomics-based knowledge about the pathophysiological role of mitochondria in the pathogenesis of type 2 diabetes will be discussed