|
|
Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0236.
 Previous Article | Table of Contents | Next Article 
Blood, 1 July 2002, Vol. 100, No. 1, pp. 178-183
IMMUNOBIOLOGY
Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic
anemia and paroxysmal nocturnal hemoglobinuria measured by V
CDR3 spectratyping and flow cytometry
Antonio M. Risitano,
Hoon Kook,
Weihua Zeng,
Guibin Chen,
Neal S. Young, and
Jaroslaw P. Maciejewski
From the Hematology Branch, National Heart, Lung and
Blood Institute, National Institutes of Health, Bethesda, MD.
We have hypothesized that in aplastic anemia (AA) the presence of
antigen-specific T cells is reflected by their contribution to the
expansion of a particular variable beta chain (V ) subfamily and also
by clonal CDR3 skewing. To determine the role of disease-specific "signature" T-cell clones in AA, we studied preferential V usage by flow cytometry and analyzed V-CDR3 regions for the presence of
oligoclonality. We first established the contribution of each V
family to the total CD4+ and CD8+ lymphocyte
pool; in AA and paroxysmal nocturnal hemoglobinuria, a seemingly random
overrepresentation of different V families was observed. On average,
we found expansion in 3 (of 22 examined) V families per patient.
When the contribution of individual V families to the effector pool
was examined, more striking V skewing was found. V-CDR3 size
distribution was analyzed for the expanded V families in isolated
CD4+ and CD8+ populations; underrepresented
V families displayed more pronounced CDR3 skewing. Expanded
CD4+V subfamilies showed mostly a polyclonal CDR3 size
distribution with only 38% of skewing in expanded V families. In
contrast, within overrepresented CD8+V types, marked
CDR3 skewing (82%) was seen, consistent with nonrandom expansion of
specific CD8+ T-cell clones. No preferential expansion of
particular V families was observed, in relation to HLA-type. In
patients examined after immunosuppressive therapy, an abnormal
V-distribution pattern was retained, but the degree of expansion of
individual V was lower. As V skewing may correlate with relative
V size, oligoclonality in combination with numerical V expansion
can be applied to recognition of disease-specific T-cell receptors.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. W. Wlodarski, Z. Nearman, A. Jankowska, N. Babel, J. Powers, P. Leahy, H.-D. Volk, and J. P. Maciejewski
Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia
J. Leukoc. Biol.,
March 1, 2008;
83(3):
589 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gargiulo, S. Lastraioli, G. Cerruti, M. Serra, F. Loiacono, S. Zupo, L. Luzzatto, and R. Notaro
Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria
Blood,
June 1, 2007;
109(11):
5036 - 5042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Wlodarski, L. P. Gondek, Z. P. Nearman, M. Plasilova, M. Kalaycio, E. D. Hsi, and J. P. Maciejewski
Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome
Blood,
October 15, 2006;
108(8):
2632 - 2641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Battiwalla, T. Hahn, M. Radovic, H. Roy, A. Wahab, E. Duman, R. Bajwa, S. Padmanabhan, J. Becker, A. J. Barrett, et al.
Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence
Blood,
March 1, 2006;
107(5):
1970 - 1973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Poggi, S. Negrini, M. R. Zocchi, A.-M. Massaro, L. Garbarino, S. Lastraioli, L. Gargiulo, L. Luzzatto, and R. Notaro
Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors
Blood,
October 1, 2005;
106(7):
2399 - 2408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Sloand, L. Mainwaring, M. Fuhrer, S. Ramkissoon, A. M. Risitano, K. Keyvanafar, J. Lu, A. Basu, A. J. Barrett, and N. S. Young
Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome
Blood,
August 1, 2005;
106(3):
841 - 851.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Terrazzano, M. Sica, C. Becchimanzi, S. Costantini, B. Rotoli, S. Zappacosta, F. Alfinito, and G. Ruggiero
T cells from paroxysmal nocturnal haemoglobinuria (PNH) patients show an altered CD40-dependent pathway
J. Leukoc. Biol.,
July 1, 2005;
78(1):
27 - 36.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ruggiero, G. Terrazzano, C. Becchimanzi, M. Sica, C. Andretta, A. M. Masci, L. Racioppi, B. Rotoli, S. Zappacosta, and F. Alfinito
GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation
J. Leukoc. Biol.,
September 1, 2004;
76(3):
634 - 640.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lu, A. Basu, J. J. Melenhorst, N. S. Young, and K. E. Brown
Analysis of T-cell repertoire in hepatitis-associated aplastic anemia
Blood,
June 15, 2004;
103(12):
4588 - 4593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. C. Bagby, J. M. Lipton, E. M. Sloand, and C. A. Schiffer
Marrow Failure
Hematology,
January 1, 2004;
2004(1):
318 - 336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zeng, G. Chen, S. Kajigaya, O. Nunez, A. Charrow, E. M. Billings, and N. S. Young
Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers
Blood,
January 1, 2004;
103(1):
325 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
