Human immunodeficiency virus type 1 tat protein modulates fibronectin expression in thymic epithelial cells and impairs in vitro thymocyte development.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Human immunodeficiency virus type 1 tat protein modulates fibronectin expression in thymic epithelial cells and impairs in vitro thymocyte development.

Cell Immunol. 1996 Feb 25;168(1):49-58. Unique Identifier : AIDSLINE MED/96179301
Maroder M; Scarpa S; Screpanti I; Stigliano A; Meco D; Vacca A; Stuppia L; Frati L; Modesti A; Gulino A; Genoa National Institute for Cancer Research, Biotechnology; Section, Rome, Italy.

Abstract: Infection of both lymphoid and stromal components of the thymus by human immunodeficiency virus type 1 (HIV-1) suggests that impairment of lymphocyte differentiation from early T cells progenitors in the thymus may contribute to the HIV-induced T cell depletion. Cross-talk between immature thymocyte and thymic epithelium through cell-to-cell adhesion mediated by fibronectin/receptor interaction plays a central role in driving T cell development. HIV-1 tat protein, like fibronectin, contains an RGD sequence involved in the interaction with fibronectin receptor. We demonstrated that gene transfer-mediated tat expression in thymic stroma is able to influence the in vitro maturation of T cell progenitors as tat-expressing epithelial cells have a decreased ability to drive the generation of CD4+8+ thymocytes from CD4-8- precursors. Furthermore, tat-expressing cells produce more fibronectin and display upregulation of VLA-5 cell surface receptor levels compared to control cells, while alpha v expression was unchanged. Cellular distribution of fibronectin is also influenced by tat. Fibronectin is distributed in the whole cell surface and along cell processes in control cells whereas it is mainly concentrated in the intracytoplasmic area in tat-expressing cells. Therefore, expression of tat in thymic epithelial cells impairs thymocyte maturation and modulates fibronectin expression: this suggests a crucial role of this viral protein in regulating the T lymphocyte differentiation program through modulation of intrathymic lympho-stromal interactions.

Keywords: Animal Antibodies, Monoclonal Cell Differentiation/DRUG EFFECTS/IMMUNOLOGY Cell Line Epithelium/IMMUNOLOGY/METABOLISM Fibronectins/*BIOSYNTHESIS/DRUG EFFECTS/IMMUNOLOGY Gene Products, tat/IMMUNOLOGY/METABOLISM/*PHARMACOLOGY Human HIV-1/*IMMUNOLOGY Male Mice Mice, Inbred C57BL Receptors, Fibronectin/BIOSYNTHESIS Support, Non-U.S. Gov't T-Lymphocytes/DRUG EFFECTS/*METABOLISM Thymus Gland/CYTOLOGY JOURNAL ARTICLE
960730
M9670511

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