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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0236.
Submitted January 25, 2002
Accepted February 26, 2002
OLIGOCLONAL AND POLYCLONAL CD4 AND CD8 LYMPHOCYTES IN APLASTIC ANEMIA AND PAROXYSMAL NOCTURNAL HEMOGLOBINURIA MEASURED BY Vß CDR3 SPECTRATYPING AND FLOW CYTOMETRY
Antonio M Risitano*, Hoon Kook, Weihua Zeng, Guibin Chen, Neal S Young, and Jaroslaw P Maciejewski
* Corresponding author; email: risitana{at}nhlbi.nih.gov.
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 (Vß) subfamily and also by clonal CDR3 skewing. To determine the role of disease-specific "signature" T-cell clones in AA, we studied preferential Vß-usage by flow cytometry and analyzed Vß-CDR3 regions for the presence of oligoclonality. We first established the contribution of each Vß family to the total CD4+ and CD8+ lymphocyte pool; in AA and PNH, a seemingly random over-representation of different Vß families was observed. On average, we found expansion in 3 (out of 22 examined) Vß families per patient. When the contribution of individual Vß families to the effector pool was examined, more striking Vß-skewing was found. Vß-CDR3 size distribution was analyzed for the expanded Vß families in isolated CD4+ and CD8+ populations; under-represented Vß families displayed more pronounced CDR3 skewing. Expanded CD4+Vß subfamilies showed mostly a polyclonal CDR3 size distribution with only 38% of skewing in expanded Vß families. In contrast, within over-represented CD8+Vß types, marked CDR3 skewing (82%) was seen, consistent with non-random expansion of specific CD8+ T-cell clones. No preferential expansion of particular Vß families was observed, in relation with HLA-type. In patients examined before and after immunosuppressive therapy, an abnormal Vß-distribution pattern was retained, but the degree of expansion of individual Vß was lower. As Vß-skewing may correlate with relative Vß size, oligoclonality in combination with numerical Vß expansion can be applied to recognition of disease-specific TCR.
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