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

Abstract EN

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.