Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Abstract

Antibodies directed against the beta chain of the T cell receptor (anti-Vbeta antibodies) are useful to identify the Vbeta repertoire of T cells in various diseases and to quantify numbers of Vbeta-bearing T cells. The goals of this study were to identify Vbeta+ cases of leukemic phase cutaneous T cell lymphoma (CTCL) and to compare the percentage of positive calls with other measures of blood tumor burden, i.e., lymphocyte subsets with a CD4+CD7- and CD4+CD26- phenotype and Sezary cell counts. Thirty-three of 49 (67%) cases of leukemic CTCL reacted with an anti-Vbeta antibody. When combined with reports from the literature, the frequency of Vbeta5 (probably Vbeta5.1) usage was relatively high when compared with Vbeta2 that is also frequently expressed by normal CD4+ T cells. The percentage of Vbeta+ cells correlated to the percentage of CD4+CD7- and CD4+CD26- cells for cases in which the neoplastic cells were deficient in expression of CD7 and CD26, respectively, but not the Sezary cell count. We hypothesize that the increased Vbeta5.1 usage in CTCL may be the result of depletion of Vbeta2 and other Vbeta-bearing T cells by staphylococcal superantigens prior to neoplastic transformation, resulting in a relative increase in the frequency of Vbeta5.1 usage in CTCL.

The role of 9-O-acetylated ganglioside D3 (CD60) and 4 1 (CD49d) expression in predicting the survival of patients with Sezary syndrome

“…Moreover, several TCR Vβ families were constantly under-represented in SS (TCR-Vβ 3, 4, 9, 14, 16, 18 and 21.3), thus defining another distinctive marker of this extranodal T-cell lymphoma. Similar results were observed by Vonderheid et al 38 although there were no TCR-Vβ2 positive cases in their cohort. There are at least 65Vβ segments in the human TCR beta V (TRVB) locus located on chromosome 7 at band 7q34.…”

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

“…This finding is important because, for decades, SEs have been suspected to play a tumor-promoting role in CTCL. 39,40,45,50,[68][69][70] We now propose that SEA-mediated cross talk between malignant and nonmalignant T cells triggers oncogenic STAT3 activation in vivo. Our findings provide a plausible explanation for clinical observations indicating that SE-producing staphylococci promote tumor growth and aggravate the disease and, conversely, that antibiotic therapy may halt disease progression and even induce tumor regression in some CTCL patients.…”

Accurate detection of the tumor clone in peripheral T-cell lymphoma biopsies by flow cytometric analysis of TCR-Vβ repertoire

“…Furthermore, analysis in biopsies is more adapted to unambiguous identification of the malignant T-cell clone since, as mentioned previously, clonal circulating T cells are frequently observed in non-malignant conditions, leading to potential confusion between reactive and tumor cells. 17 On the basis of the promising results obtained from blood samples, [11][12][13][14][15][16] we used flow cytometry to assess the expression of 25 Vb chain members of the TCR. Indeed, T-cell clones use a single Vb domain and can thus be identified by the abnormal expansion of one Vb family or by a restricted TCR-Vb repertoire (see Materials and methods).…”

“…In addition, preferential use of some Vb families has been reported in leukemic phase of cutaneous T-cell lymphoma 16 and T-CD4 þ large granular lymphocytic proliferations in which the clone specificity for hCMV peptides has been demonstrated. 11,39 By contrast, Lima et al 11 reported that CD8 þ T-cell large granular lymphocytic proliferations in blood samples showed a pattern of Vb distribution that mimics the frequency at which individual Vb families are represented in normal CD8 þ T cells, suggesting that CD8 þ T-cell large granular lymphocytic leukemia cells were clonally transformed in a random manner.…”

“…This technique has proved useful in detecting malignant T cells in peripheral blood samples from patients with diverse mature T-cell leukemias. [11][12][13][14][15][16] T-cell clones use the same V domain, and are thus detected by an overexpressed V family (direct identification) or by a restricted V repertoire if they are not recognized by the 25 anti-V antibodies of the panel (indirect identification). However, T-cell clone analysis in blood samples is not optimal for peripheral T-cell lymphomas, as (1) there may be no circulating lymphoma cells, (2) malignant circulating cells may not precisely reflect the clone at the site of tumor involvement and (3) when present, clonal subsets are not always malignant, as observed in infectious or autoimmune conditions, as well as in elderly people.…”