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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0236.
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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.
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