HTLV-1 Propels Untransformed CD4 Lymphocytes into the Cell Cycle While Protecting CD8 Cells from Death

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2006 Apr 6

PMID 16585963

Citations 33

Authors

David Sibon

Anne-Sophie Gabet

Marc Zandecki

Christiane Pinatel

Julien Thete

Marie-Helene Delfau-Larue

Samira Rabaaoui

Antoine Gessain

Olivier Gout

Steven Jacobson

Franck Mortreux

Eric Wattel

Affiliations

Soon will be listed here.

Abstract

Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8+ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms--infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones.

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