TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis

Abstract

The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long-standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed.

gammadelta T cell subsets in patients with arthritis and chronic neutropenia

“…32 Although this is the first description of γδ T cell lymphoproliferations in psoriatic arthritis, Kuipers et al described, a neutropenic patient with RA and ankylosing spondylitis whose γδ T cell lymphoproliferations used Vδ genes other than Vδ1, and Vγ genes other than Vγ2. 19 Together, these data suggest that γδ T cell lymphoproliferations associated with spondyloarthropathies may selectively involve Vγ2 − /Vδ1 − /Vδ2 − γδ clones. Thus definitions of the balance of γδ and other T cell subsets in neutropenic patients may have diagnostic and prognostic implications.…”

“…1 12 13 19 An additional patient described by the latter authors, as discussed below in further detail, had an expansion of cells expressing another "unconventional" (Vγ2 − /Vδ1 − ) TCR. 19 Collectively, therefore, the data suggest the paradigm that γδ T cell lymphoproliferations in patients with FS or PFS derive from lymphocytes that are not usually expanded by common antigens from micro-organisms, but rather from other subsets whose antigenic targets have not yet been identified. In this regard patient 2 is exceptional, since her lymphoproliferations do use a Vγ2 + /Vδ2 + TCR (fig 1).…”

“…15 Sporadic studies have shown, furthermore, that lymphoproliferations of γδ T cells, rather than CD3 + CD8 + TCRαβ + T cells may occur in a minority of patients with FS/PFS. [17][18][19][20][21] The specific functional repertoires of the different subsets of γδ T cells suggest they may potentially have beneficial or detrimental roles in disease manifestations in patients with neutropenia and arthritis-for example, by secreting cytokines after interacting with pathogenic micro-organisms, or by influencing antibody production. 1 2 In this study we examined the relation between the characteristics of the clinical syndrome and the nature of the specific subset undergoing expansion in patients with chronic neutropenia and arthritis.…”

Rheumatoid arthritis and malignancies

“…Чтобы ус-тановить диагноз лейкоза из больших гранулярных лим-фоцитов, необходимо доказать клональность пролифера-ции CD8+ Т-клеток на основании реарранжировки ге-нов Т-клеточного рецептора методом ПЦР (чувствитель-ность 70-80%) или Саузерн-блоттинг (Southern blot) гиб-ридизации (имеет меньше ложных результатов) [26]. В большинстве случаев Т-клеточного лейкоза представ-лена клональная реарранжировка αβ-цепи Т-клеточного рецептора, однако описаны пациенты с рестрикцией γδ-цепи [38,39].…”