IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II.
Human T cell leukemia virus type I (HTLV-I) is etiologically associated with adult T cell leukemia (ATL) and chronic neurological disease, tropical spastic paraparesis (TSP). In our study, a unique IL-2 dependent human T cell line, designated TY8-3, was established from a thymoma obtained from a myasthenia gravis patient. The cells were heterogeneous and mainly consisted of those with CD4 , CD8 as well as activation markers and adhesion molecules including IL-2Ralpha,beta,gamma, CD45RO, Tf-R, HLA-DR, LFA-1alpha,beta, LFA-3, ICAM-1 and OX40 but without CD3 surface markers. Furthermore, these cells underwent an efficient and reproducible IL-2 independent transformation upon cocultivation with HTLV-I/II producing cell lines. Interestingly, although the infected cells became IL-2 independent, the growth rate of infected cells was significantly lower than those of parental TY8-3 cells. Clonal HTLV-I proviral DNA and viral particles were detected in the cells. Down-regulation of the lck and fyn genes and activation of the lyn gene was demonstrated in the IL-2 independent HTLV-positive TY8-3 cells. Subclones of TY8-3 cells were again able to be efficiently transformed and became IL-2 independent several months after coculture. Our results thus exhibit that TY8-3 cells and its subclones provide us with a very unique model whereby IL-2 independent transformation events of human T cells by HTLV-I/II in vitro can be studied at a clonal level.
Yoshida
T
T
Biophenix Co., Ltd., Ube Yamaguchi, Japan.
Miyagawa
E
E
Yamaguchi
K
K
Kobayashi
S
S
Takahashi
Y
Y
Yamashita
A
A
Miura
H
H
Itoyama
Y
Y
Yamamoto
N
N
D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D015536:Down-Regulation; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D008854:Microscopy, Electron; D009157:Myasthenia Gravis / Q000378:metabolism; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D013945:Thymoma / Q000378:metabolism; D013997:Time Factors; D019061:src-Family Kinases
D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases