Quantitative tracking of T cell clones after haematopoietic stem cell transplantation

Abstract

Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood. Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use it to perform the first detailed, quantitative tracking of T cell clones during 10 months after transplantation. We show that multiple clones survive the procedure, contribute to the immune response to activated infections, and form a new skewed and stable T cell receptor repertoire.

Distinctive properties of identical twins' TCR repertoires revealed by high-throughput sequencing

“…TCR repertoires (for α and β chains) were obtained for all three pairs of monozygous twins. Sequencing libraries were prepared as described previously (12,15,23) with several modifications (Fig. S1 and SI Materials and Methods).…”

“…Some of these studies reported the common use of particular V genes and common clonotypes. In recent years, the high-throughput sequencing technologies paved the way to whole-repertoire studies of individual TCRs that led to new findings in the field of adaptive immunity (1,5,6,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In this study, for the first time to the best of our knowledge, we obtain and compare the α and β chain TCR repertoires of three pairs of MZ twins using next-generation sequencing (NGS).…”

Quantitative Profiling of Immune Repertoires for Minor Lymphocyte Counts Using Unique Molecular Identifiers

“…ecently developed high-throughput sequencing (HTS) methods for adaptive immunity studies allowed for the deep and, to a certain extent, quantitative analysis of clonotypic composition of TCR (1)(2)(3)(4) and BCR (5-9) diversity.…”

“…These methods enabled researchers to decipher the intimate architecture of immune repertoires in health and disease, both at the general scale (1)(2)(3)(4)(10)(11)(12)(13)(14)(15)(16)(17) and in diverse lymphocyte subpopulations, such as naive and memory T cells (10,11,18), functional subsets of CD4 + T cells (19,20) or B cells (5,8), NKT and mucosal-associated invariant T cells subsets (21)(22)(23), tumor-infiltrating lymphocytes (24,25), tissue-specific lymphocytes (26), or Ag-specific T cells (20).…”

First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy

“…Several studies have demonstrated that CD34 þ selection of the graft does not increase the effectiveness of HSCT for treating autoimmune diseases 2,10,11 but increases the risk of secondary autoimmune diseases 12 and infectious complications, 13 --16 especially for heavily pretreated patients. 17 Thus, we believe that the effectiveness of HSCT for treating autoimmune diseases is not the result of the complete elimination of autoimmune cells, 5,9,18 and elimination of all immune cells, which would require both CD34 þ selection and increased doses of cytotoxic chemotherapy, 19 should not be the aim of HSCT protocols. At the same time, the 'complex reprogramming' of the immune system after HSCT that results in the suppression of the autoimmune process remains vaguely defined.…”