The following is a summary of “Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation,” published in the JANUARY 2023 issue of Allergy & Immunology by Labrosse, et al.
To survive, rare hereditary immune illnesses called severe combination immunodeficiencies (SCID) must be permanently treated with hematopoietic cell transplantation (HCT) or gene therapy. Despite the effectiveness of allogeneic HCT, many SCID patients had poor long-term prognoses, chronic T-cell lymphopenia, and inadequate immune reconstitution. In previously transplanted SCID patients, CD4+ T-cell lymphopenia may be linked to a condition known as T-cell fatigue.
At a median of 10.4 years following HCT, blood samples from 61 SCID patients were examined for signs of tiredness.
Patients with inadequate T-cell reconstitution had lower frequencies of naïve CD45RA+/CCR7+ T cells, recent thymic emigrants, and TCR excision circles than post-HCT SCID patients with normal CD4+ T-cell numbers. They also showed signs of T-cell fatigue and abnormal activation, including a limited TCR repertoire, increased expression of inhibitory receptors (PD-1, 2B4, CD160, BTLA, CTLA-4), and increased expression of activation markers (HLA-DR, perforin). Inverse correlations were found between the CD4+ T-cell count, recent thymic emigrants, TCR excision circles, and TCR diversity and the exhaustion score of CD8+ T cells. Receivers of unconditioned HCT had higher levels of exhaustion, particularly when they were further away from the HCT. Patients with lower CD4+ T cell counts displayed a transcriptional exhaustion signature.
Patients who received unconditioned HCT for SCID may have late post-HCT T-cell depletion due to decreased T-lineage cell generation. Their T cells’ increased production of inhibitory receptors may serve as a diagnostic for inadequate long-term T-cell reconstitution.
Reference: jacionline.org/article/S0091-6749(22)01057-0/fulltext