Selective reduction of natural killer T cells in the bone marrow of aplastic anaemia
Weihua Zeng, Jaroslaw P Maciejewski, Guibin Chen, Antonio M Risitano, Martha Kirby, Sachiko Kajigaya, Neal S Young, Weihua Zeng, Jaroslaw P Maciejewski, Guibin Chen, Antonio M Risitano, Martha Kirby, Sachiko Kajigaya, Neal S Young
Abstract
T cell-mediated suppression of haematopoiesis is believed to play an important role in the pathophysiology of aplastic anaemia (AA) and in the pancytopenia of some myelodysplastic syndromes (MDS). Natural-killer T (NKT) cells belong to a unique lymphocyte subset that expresses an invariant T-cell receptor (TCR), consisting of Valpha24JalphaQ, and common NK cell surface markers. NKT cells have been hypothesized to play a role in immune regulation, and many human autoimmune conditions are associated with NKT cell deficiency. Here we investigate the role of NKT cells in AA and MDS patients. Flow cytometry demonstrated that NKT cells, unlike other T-lymphocyte subpopulations, were disproportionally decreased in AA and MDS marrow. When we compared variability within the CDR3 region of Valpha24 in CD4-CD8- T cells derived from AA and healthy individuals, the CDR3 size of Valpha24 cells showed a polyclonal distribution in AA patients, while in control subjects a typical oligoclonal or monoclonal pattern was found. Southern blot and sequence analysis of Valpha24 polymerase chain reaction products revealed that the NKT cell-specific JalphaQ region was predominant in control subjects, whereas it was not, or only very weakly, detected in AA and MDS patients. These results show that NKT cells are profoundly decreased in AA and MDS, and their deficiency may, as in other human autoimmune diseases, play a role in the local immune dysregulation in AA and MDS.
Source: PubMed