Regulatory T-cell function of adult T-cell leukemia/lymphoma cells.
Adult T-cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4(+)CD25(+)FOXP3(+) Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo-responsive to T-cell receptor-mediated activation, but also suppress the proliferation of autologous CD4(+) non-ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN-gamma, and suppress IFN-gamma production by autologous CD4(+) non-ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e., how HTLV-1-infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state.
Yano
Hiroki
H
Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan.
Ishida
Takashi
T
Inagaki
Atsushi
A
Ishii
Toshihiko
T
Kusumoto
Shigeru
S
Komatsu
Hirokazu
H
Iida
Shinsuke
S
Utsunomiya
Atae
A
Ueda
Ryuzo
R
D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
C515354:CCR4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D007371:Interferon-gamma