Long-Term Culture and T Cell Receptor Analysis of T Cell Clones Isolated from a Patient with Adenosine Deaminase Deficiency and Type I Diabetes

Abstract

We performed limiting dilution culture of T cells from a patient affected by primary immunodeficiency as a result of complete lack of adenosine deaminase (ADA) activity and also affected by insulin-dependent diabetes mellitus (type I diabetes). Despite the occurrence of immunodeficiency, we were able to raise and grow T cell clones derived from this patient in long-term culture. These T cells displayed ADA enzymatic activity and produced interleukin-2 after engagement of their T cell receptor (TCR)/CD3 complex. We analyzed the TCR repertoire of such clones by nucleotide sequencing of TCR β chains. The results show that the T cell clones express different Vβ but similar J regions. However, the CDR3 regions which are implicated in antigen recognition were found to be heterogeneous.