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Development of a Method of Thymocyte Differentiation of Bone Marrow-Enriched CD34⁺CD38^– Cells in Postnatal Allogeneic Cultured Thymic Epithelia to Evaluate Immunodeficiency Disorders

^a Pediatric Research Institute and
^b Department of Pathology, St. Louis University Health Sciences Center, St. Louis, Missouri, USA

Key Words. CD34⁺ • Thymocyte maturation in vitro • Cultured thymic epithelia • Human immunodeficiency virus

Correspondence: Dr. Alan P. Knutsen, Pediatric Research Institute, St. Louis University Health Sciences Center, 3662 Park Avenue, St. Louis, MO 63110, USA.

An in vitro model of CD34⁺CD38^– stem cell (SC) differentiation in postnatal cultured thymic epithelia fragment (CTEF) cocultures is described. Sequential phenotypic analysis of the progeny of the SC-CTEF demonstrated predominantly thymocytes and minor populations of promyelocytes, monocytes and natural killer cells. Triple-positive CD3⁺CD4⁺CD8⁺, double-positive CD4⁺CD8⁺, and mature single-positive CD4⁺ and CD8⁺ T cells, which were TCRß⁺, were identified indicating normal thymocyte maturation. In kinetic studies, mature single-positive CD4⁺ T cells increased from 29% of total cells at one week to 54% at four weeks of coculture. These findings demonstrate that coculture of bone marrow-derived SC and allogeneic cultured thymic epithelia in vitro results in continuous normal predominantly thymocyte differentiation. The SC-CTEF cocultures were then infected with two different strains of human immunodeficiency virus. CD4⁺ thymocytes were markedly decreased. However, inhibition of early thymocyte maturation steps was also suggested by the presence of increased triple-negative and CD44⁺CD25^–CD3^– thymocytes and decreased CD44⁺CD25⁺ thymocytes. This model system of thymocyte maturation will be useful in the evaluation of primary T cell immunodeficiency disorders, gene therapy of SC and pharmacological augmentation of thymic function.

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