Characterizing T Cells in SCID Patients Presenting with Reactive or Residual T Lymphocytes

Introduction. Patients with severe combined immunodeficiency (SCID) may present with residual circulating T cells. While all cells are functionally deficient, resulting in high susceptibility to infections, only some of these cells are causing autoimmune symptoms. Methods. Here we compared T-cell functions including the number of circulating CD3+ T cells, in vitro responses to mitogens, T-cell receptor (TCR) repertoire, TCR excision circles (TREC) levels, and regulatory T cells (Tregs) enumeration in several immunodeficinecy subtypes, clinically presenting with nonreactive residual cells (MHC-II deficiency) or reactive cells. The latter includes patients with autoreactive clonal expanded T cell and patients with alloreactive transplacentally maternal T cells. Results. MHC-II deficient patients had slightly reduced T-cell function, normal TRECs, TCR repertoires, and normal Tregs enumeration. In contrast, patients with reactive T cells exhibited poor T-cell differentiation and activity. While the autoreactive cells displayed significantly reduced Tregs numbers, the alloreactive transplacentally acquired maternal lymphocytes had high functional Tregs. Conclusion. SCID patients presenting with circulating T cells show different patterns of T-cell activity and regulatory T cells enumeration that dictates the immunodeficient and autoimmune manifestations. We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency. 1. Introduction Severe combined immunodeficiency (SCID) is typically characterized by significantly low number and/or defective function of T and B cells. In some cases, T cells may present, as a result of residual autologous cells or transplacentally acquired maternal lymphocytes [1]. Residual autologous T cells are usually emerging from partial thymic maturation impairment such as in the case of Major histocompatibility complex class II (MHC-II) deficiency. MHC-II molecules drive the development, activation, and homeostasis of CD4+ T-helper cells. It is thus not surprising that the absence of MHC-II expression results in a severe primary immunodeficiency disease. Yet, the residual cells in MHC-II deficient patients are considered as nonreactive; therefore patients typically do not display significant autoimmune phenomena. Although immunity is extensively impaired in such cases, regulatory tolerance mechanisms are not known to be affected [2]. Moreover, while the mainstay of the diagnosis of MHC-II deficiency is the