|T cell depletion in HIV-1 infection: how CD4+ cells go out of stock.|| ||Mette D et al.
| ||“HIV-1 infects CD4+ T cells but direct infection and killing of these cells can only partly account for HIV-1-associated lymphocyte depletion. The actual number of productively infected cells is estimated to be relatively low, in the order of 5 X 10^7 to 5 X 10^8 CD4+ T cells whereas the human body contains an average of 2.5 X 10^11 CD4+ T cells. Direct infection of CD4+ T cells does not explain the loss of naive CD8+ T cells that parallels the decline in naive CD4+ T cells during asymptomatic HIV-1 infection.”|
| ||Nature Immunology. 2000 Oct;1:285-9.||2000|
|HIV-induced decline in blood CD4/CD8 ratios: viral killing or altered lymphocyte trafficking?|| ||Rosenberg YJ, Anderson AO, Pabst R.
| ||“During HIV infection, CD4+-cell numbers and CD4/CD8 ratios decline in the blood. This is usually attributed to direct viral killing or to other indirect mechanisms. However, current models generally assume that such changes in the blood are representative of changes in total CD4+-cell numbers throughout the body. This article discusses the importance of alterations in CD4+- and CD8+-cell migration in regulating blood lymphocyte levels and questions the extent of virus-mediated CD4+-cell destruction”|
| ||Immunology Today. 1998;19:10-17.||1998|
|Rapid CD4+ T-cell turnover in HIV-1 infection: a paradigm revisited.|| ||Wolthers KC et al.
| ||“Although progression to AIDS has generally been believed to be related to exhaustion of the capacity for CD4+ T-cell renewal due to persistently enhanced CD4+ T-cell turnover, this view is now increasingly being challenged. This paper discusses these new experimental findings and proposes alternative explanations for CD4+ T-cell depletion in human HIV-1 infection.”|
| ||Immunology Today. 1998;19:44-48.||1998|
|Conservation of total T-cell counts during HIV infection: alternative hypotheses and implications.|| ||Grossman Z et al.
| ||“Margolick...and, independently, Adleman and Wofsy proposed the BH [Blind Homeostasis] hypothesis. They postulated that, normally, a constant number of T lymphocytes is maintained regardless of the CD4-toCD8 ratio...[and] would necessarily lead to a progressive depletion of the CD4 compartment in HIV infection if CD4 cells are preferentially destroyed by the virus...[based on the detailed analysis in this paper] we consider the original BH hypothesis and also its more elaborate version to be biologically rather implausible...If correct, the BH hypotheses, but not the alternative hypothesis, could account for CD4 cell depletion by HIV. However, as we have discussed, there is no compelling evidence in favor of BH, either inherent or HIV imposed...these considerations also suggest a need to reevaluate current concepts about HIV pathogenesis, including the concept that a systemic depletion of CD4 T cells is the hallmark of the disease.”|
| ||JAIDS. 1998;17(5):450-7.||1998|
|T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover.|| ||Wolthers KC, Bea G, Wisman A, Otto SA, de Roda Husman AM, Schaft N, de Wolf F, Goudsmit J, Coutinho RA, van der Zee AG, Meyaard L, Miedema F.
| ||Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8(+) T cell TRF length decreased but CD4(+) T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8(+) T cells, but not in CD4(+) T cells. These results are compatible with CD4(+) T cell decline in HIV-1 infection caused by interference with cell renewal.|
| ||Science. 1996 Nov 29;274(5292):1543-7||1996|