Upregulation of Gfi-1, a gene involved in IL-2-independent growth of T cells, in a murine retrovirus-induced immunodeficiency syndrome.
BACKGROUND
A prominent feature of retrovirus-induced immunodeficiency in mice (MAIDS) is early polyclonal activation of CD4+ T cells followed by the appearance of monoclonal lymphomas marked by clonal proviral integrations. These events appear to occur independent of interleukin-2 (IL-2), suggesting the activity of an alternative growth-promoting pathway. We studied the possible contributions to T cell expansion of a gene, Gfi-1, previously shown to confer IL-2 independence to rat T cell lymphomas.
We studied 17 mice with MAIDS that had clonal populations of T cells. Proviral integrations at Gfi-1 were detected in two animals. These integrations were associated with enhanced transcription of Gfi-1. Unexpectedly, elevated levels of Gfi-1 transcripts were also observed in four T cell lymphomas without detectable integrations at this locus. This suggests that IL-2-independent T cell growth in MAIDS may be driven by transcriptional activation of Gfi-1 by proviral insertion or transactivation.
Liao
X
X
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA.
Tang
Y
Y
Chattopadhyay
S K
SK
Hartley
J W
JW
Morse
H C
HC
D000818:Animals; D015139:Blotting, Southern; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000821:virology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D015321:Gene Rearrangement; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D016296:Mutagenesis / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000276:immunology; D016335:Zinc Fingers / Q000235:genetics
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; C498276:Gfi1 protein, rat; D007376:Interleukin-2; D014157:Transcription Factors