An extensive flow cytometric evaluation continues of patients with autoimmune lymphoproliferative syndrome (ALPS) and their extended family members, on the basis of characterization of the expanded double-negative T-cell and B-cell populations. Double-negative T-cells have been demonstrated to be alpha beta TcR, CD57+, HLA-DR+, and CD45RA+. This study has been extended to characterize the double-negative T-cells more completely including B220 expression and gamma-delta TcR T-cells in all ALPS patients. In addition, we have initiated expanded characterization of the B cells, directed at memory B cells using CD27 and B220 assessment in these patients. The observations in the B cells of ALPS patients are tied directly to an additional active protocol directed at the assessment of B220 expression on human lymphocytes. The relative deficiency in CD4/CD25 T cells that we have identified has resulted in the initiation of functional studies directed at this T cell subpopulation to assess if the immunophenotypic findings represent a functional defect in immunoregulatory T cells that could explain the genotype phenotype disparity in families with ALPS type 1a. This approach has met with unanticipated problems in developing a consistent ex vivo indicator system for inhibition. It does appear that the assay system is now set and the studies of immunoregulatory T cells in ALPS should be completed in the next FY. In addition, this assay system will be extended to ATL cells as a possible leukemic expansion of the immunoregulatory T cell.
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