The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with HTLV-I.
OBJECTIVE
In a recent study to purify adult T-cell leukemia-lymphoma (ATL) cells from acute-type patients by flow cytometry, three subpopulations were observed in a CD3 versus CD7 plot (H: CD3(high)CD7(high); D: CD3(dim)CD7(dim); L: CD3(dim)CD7(low)). The majority of leukemia cells were enriched in the L subpopulation and the same clone was included in the D and L subpopulations, suggesting clonal evolution. In this study, we analyzed patients with indolent-type ATL and human T-cell leukemia virus type I (HTLV-I) asymptomatic carriers (ACs) to see whether the CD3 versus CD7 profile reflected progression in the properties of HTLV-I-infected cells.


METHODS
Using peripheral blood mononuclear cells from patient samples, we performed multi-color flow cytometry. Cells that underwent fluorescence-activated cell sorting were subjected to molecular analyses, including inverse long PCR.


RESULTS
In the D(%) versus L(%) plot, patient data could largely be categorized into three groups (Group 1: AC; Group 2: smoldering- and chronic-type ATL; and Group 3: acute-type ATL). Some exceptions, however, were noted (e.g., ACs in Group 2). In the follow-up of some patients, clinical disease progression correlated well with the CD3 versus CD7 profile. In clonality analysis, we clearly detected a major clone in the D and L subpopulations in ATL cases and, intriguingly, in some ACs in Group 2.


CONCLUSIONS
We propose that the CD3 versus CD7 plot reflects progression of disease stage in patients infected with HTLV-I. The CD3 versus CD7 profile will be a new indicator, along with high proviral load, for HTLV-I ACs in forecasting disease progression.
Division of Molecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Seiichiro
S
Kobayashi
Yamin
Y
Tian
Nobuhiro
N
Ohno
Koichiro
K
Yuji
Tomohiro
T
Ishigaki
Masamichi
M
Isobe
Mayuko
M
Tsuda
Naoki
N
Oyaizu
Eri
E
Watanabe
Nobukazu
N
Watanabe
Kenzaburo
K
Tani
Arinobu
A
Tojo
Kaoru
K
Uchimaru
D000328:Adult; D000368:Aged; D019011:Antigens, CD7 / Q000737:chemistry / Q000378:metabolism*; D058345:Asymptomatic Infections; D017252:CD3 Complex / Q000737:chemistry / Q000378:metabolism*; D003116:Color; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012307:Risk Factors; D019562:Viral Load
D019011:Antigens, CD7; D017252:CD3 Complex