Monoclonal TCR-Vβ13.1+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin

Abstract

Monoclonal TCR␣␤ ؉ /CD4 ؉ T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-V␤ repertoire. In the present study we explored the potential association between the expanded TCR-V␤ families, the CDR3 sequences of the TCR-V␤ gene, and the HLA genotype of patients with monoclonal TCR␣␤ ؉ /CD4 ؉ T-LGL lymphocytosis.

Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens

“…2 These findings suggest that the expansion of (mono)clonal T cells in these patients might result from antigenic stimulation through a common peptide. In contrast to cytotoxic CD8 ϩ T lymphocytes, the exact role of CD4 ϩ T cells bearing a cytotoxic immunophenotype in the clearance of viral infections has remained unclear for decades.…”

“…In addition, these cases show a high degree of homology in the CDR3 region of the TCR-␤ chain, supporting the existence of a common chronic antigen-driven origin for this monoclonal CD4 ϩ T-LGL lymphoproliferative disorder. 2 However, in contrast to other T-LGL neoplasias (eg, TCR-␥␦ ϩ and CD8 ϩ TCR-␣␤ ϩ T-LGL), 3,4 CD4 ϩ T-LGL cases did not show a clear association with autoimmune disorders, pointing out the potential involvement of non-self-antigens in this lymphoproliferative disorder. 1,2 At present, it is well established that some viruses (eg, human T-cell lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), cytomegalovirus [CMV]) are capable of establishing long-term, persistent infections with chronic immune activation and inflammation.…”

“…2 However, in contrast to other T-LGL neoplasias (eg, TCR-␥␦ ϩ and CD8 ϩ TCR-␣␤ ϩ T-LGL), 3,4 CD4 ϩ T-LGL cases did not show a clear association with autoimmune disorders, pointing out the potential involvement of non-self-antigens in this lymphoproliferative disorder. 1,2 At present, it is well established that some viruses (eg, human T-cell lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), cytomegalovirus [CMV]) are capable of establishing long-term, persistent infections with chronic immune activation and inflammation. 5 Such a latent virus could act as a source of peptides, which are presented to CD4 ϩ T-LGL cells, potentially leading to its clonal expansion.…”

“…1 Although CD4 ϩ T-LGL patients typically display an indolent clinical course, its outcome remains unknown and is frequently determined by its association with other neoplasias. 1 In a recent study, 2 we showed that monoclonal CD4 ϩ T-LGL cells display a restricted TCR-V␤ repertoire with a predominance of TCR-V␤13.1 cases, in clear association with an HLA-DRB1*0701 haplotype. In addition, these cases show a high degree of homology in the CDR3 region of the TCR-␤ chain, supporting the existence of a common chronic antigen-driven origin for this monoclonal CD4 ϩ T-LGL lymphoproliferative disorder.…”

High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia

“…1 T-LGL cases, 11 but this rare disease entity still remains poorly described. To further elucidate the pathogenesis of this rare subgroup of T-LGL leukemia, we explored the mutational landscape of CD4 ) fractions.…”