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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2809-2818
Human Immunodeficiency Virus nef Gene Expression Affects
Generation and Function of Human T Cells, But Not Dendritic Cells
Bruno Verhasselt,
Evelien Naessens,
Chris Verhofstede,
Magda De
Smedt,
Sigrid Schollen,
Tessa Kerre,
Dominique Vanhecke, and
Jean Plum
From the Department of Clinical Chemistry, Microbiology and
Immunology, University of Ghent, University Hospital of Ghent, Ghent,
Belgium; and the Flanders Interuniversity Institute for Biotechnology
(VIB), Belgium.
Human immunodeficiency virus (HIV)-infected individuals develop an
acquired immune deficiency syndrome (AIDS) due to loss in their
lymphocyte numbers and cellular defects in T cells and antigen-presenting cells (APC). HIV infection of the thymus results in
deficient replenishment of the peripheral naive T-cell pool. The HIV
nef gene was shown to be important for progression towards AIDS
and cellular depletion of the infected thymus. Here, we demonstrate by
retroviral gene transfer that nef expression, in the absence of
other HIV genes, impaired human thymic T-cell development. Thymocytes
were generated in reduced numbers and downmodulated CD4 and CD8 cell
surface expression. T cells grown from nef-expressing thymocytes were hyperproliferative in vitro upon T-cell receptor triggering. Mature dendritic cells (DC) were functional and had normal
surface CD4 levels despite nef expression. Thus, nef
expression alone may contribute to AIDS development by reduced T-cell
generation and T-cell hyperresponsiveness.
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