Use of humanized mouse models for the study of idiopathic CD4 lymphocytopenia (HUM7P.313)

Abstract

Abstract Patients with Idiopathic CD4 Lymphocytopenia (ICL) have low circulating CD4 T-cell counts and develop opportunistic diseases and papillomavirus-related dysplasia. The etiology of ICL is unknown but the low numbers of CD4 T-cells could be explained by decreased thymic production, increased cell death, and/or increased migration or retention of the T cells in secondary lymphoid organs or tissues. To distinguish between these three possibilities we set up a humanized mouse model by transferring either peripheral blood mononuclear cells (PBMC), or Hematopoietic Stem Cells (HSC) from ICL patients or healthy controls (HC) into immune-compromised mice. First, we transferred HC cells into three different strains of mice to identify the most efficient and reproducible host for the human cells. We found that NOD-RAGKO-γcKO (NRG) mice represented the best model, as one to four weeks after transferring PBMC into NRG mice, we reproducibly found human T cells in blood, spleen, lymph node and bone marrow with no graft versus host disease. We next transferred PBMC from either HC or ICL patients into NRG mice to compare survival, expansion, phenotype and migration properties of the human cells. Preliminary results show that mice that received ICL cells developed lymphocytopenia comparable to ICL patients. These data encourage further use of this humanized mouse model to identify the etiology and pathogenesis of ICL and perhaps other human immune-deficiencies that affect T-cell homeostasis.