PMID- 2367534
OWN - NLM
STAT- MEDLINE
DCOM- 19900815
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 87
IP  - 13
DP  - 1990 Jul
TI  - Transactivation of interleukin 2 and its receptor induces immune activation in 
      human T-cell lymphotropic virus type I-associated myelopathy: pathogenic 
      implications and a rationale for immunotherapy.
PG  - 5218-22
AB  - A state of T-cell activation, reflected by a marked degree of spontaneous 
      proliferation in vitro, exists among patients with human T-cell lymphotropic 
      virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis 
      (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). 
      We wished to define the mechanism by which the immune activation of circulating 
      cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this 
      HTLV-I-associated disease. By using a modification of the polymerase chain 
      reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha 
      chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I 
      transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL 
      patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha 
      transcripts was detected in HAM/TSP and seropositive carriers that paralleled the 
      coordinate mRNA expression of the pX transactivator. In addition, IL-2 and 
      soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were 
      elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, 
      transcripts for IL-2 and pX were not demonstrable in the circulating cells. 
      Finally, the marked degree of in vitro spontaneous proliferation present in 
      HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking 
      antibodies. Collectively, these results suggest that immune activation in 
      HAM/TSP, in contrast to ATL, is virally driven by the transactivation and 
      coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process 
      may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.
FAU - Tendler, C L
AU  - Tendler CL
AD  - Metabolism Branche, National Cancer Institute, National Institutes of Health, 
      Bethesda, MD 20892.
FAU - Greenberg, S J
AU  - Greenberg SJ
FAU - Blattner, W A
AU  - Blattner WA
FAU - Manns, A
AU  - Manns A
FAU - Murphy, E
AU  - Murphy E
FAU - Fleisher, T
AU  - Fleisher T
FAU - Hanchard, B
AU  - Hanchard B
FAU - Morgan, O
AU  - Morgan O
FAU - Burton, J D
AU  - Burton JD
FAU - Nelson, D L
AU  - Nelson DL
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Interleukin-2)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-2)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Southern
MH  - Female
MH  - Human T-lymphotropic virus 1/*genetics/immunology
MH  - Humans
MH  - Immunotherapy
MH  - Interleukin-2/*immunology
MH  - Leukemia-Lymphoma, Adult T-Cell/*immunology/therapy
MH  - *Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Nucleic Acid Hybridization
MH  - Oligonucleotide Probes
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - Receptors, Interleukin-2/*immunology
MH  - Reference Values
MH  - *Transcriptional Activation
PMC - PMC54293
EDAT- 1990/07/01 00:00
MHDA- 1990/07/01 00:01
PMCR- 1991/01/01
CRDT- 1990/07/01 00:00
PHST- 1990/07/01 00:00 [pubmed]
PHST- 1990/07/01 00:01 [medline]
PHST- 1990/07/01 00:00 [entrez]
PHST- 1991/01/01 00:00 [pmc-release]
AID - 10.1073/pnas.87.13.5218 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1990 Jul;87(13):5218-22. doi: 10.1073/pnas.87.13.5218.