Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

Alison Y. Swaims, Francesca Khani, Yingyu Zhang, Arthur I. Roberts, Satish Devadas, Yufang Shi, Arnold B. Rabson

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulated by the HTLV-1 LTR. T-cell receptor stimulation of LTR-Tax CD4+ T cells induced Tax expression, hyper-proliferation, and immortalization in culture. The transition to cellular immortalization was accompanied by markedly increased expression of the antiapoptotic gene, mcl-1, previously implicated as important in T-cell survival. Immortalized cells exhibited a CD4+CD25+CD3 - phenotype commonly observed in ATL. Engraftment of activated LTR-Tax CD4+ T cells into NOD/Shi-scid/IL-2Rγ null mice resulted in a leukemia-like phenotype with expansion and tissue infiltration of Tax+, CD4+ lymphocytes. We suggest that immune activation of infected CD4+ T cells plays an important role in the induction of Tax expression, T-cell proliferation, and pathogenesis of ATL in HTLV-1-infected individuals.

Original languageEnglish (US)
Pages (from-to)2994-3003
Number of pages10
JournalBlood
Volume116
Issue number16
DOIs
StatePublished - Oct 21 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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