Clinical, biological and immunophenotypical features of clonal expansions of PB TCRab/CD4+ large granular lymphocytes

• Type: Article in International Scientific Journal
• Date: 2000

Authors

Lima, M (Author) Other

Journal

Title: Blood

Vol. 96

ISSN: 0006-4971

Publisher: Elsevier

Indexing

Scopus - 0 Citations

Other information

Authenticus ID: P-008-QBD

Abstract (EN): We have analyzed the clinical, biological, immunophenotypical and functional features of a series of 20 cases (10 males/10 females, aged 65±1 ly) displaying a clonal expansion of LGL corresponding to CD4+ T-cells coexpressing both CDS and NK-associated (NKa) antigens (CD4+/NKa+/CD8-/+dim T-cells). These patients showed an indolent disease course. Except for the relatively frequent coexistence of a second neoplasia. Overall, another tumor was diagnosed in 6 patiens (30%), corresponding to a hematological disorder in 3 cases (2 B-NHL and one TCRgd T-cell leukemia) and to a solid tumor in the other 3 patients. Physical examination was normal except in the two B-NHL cases (organomegalies). The relative and absolute PB lymphocyte counts were increased (64+13% of all PB leucocytes; 7.1±6.5xl09 lymph/L); however, hemoglobin levels, platelet and neutrophyl counts, as well as serum LDH and B2-microglobulin levels were within the normal range in all patients, except in those with an associated tumor. From the phenotypical point of view, the most relevant characteristics of CD4+/NKa+/CD8-/+dim T-cells, in adition to their relatively high FSC/SSC values, were the expression of CD56 and/or CD57, (usually being CD57+/CD56+), cytoplasmic granzyme B and the frequent coexpression of CD45RA and CD45RO, together with negativity for CD28. The study of the Vbeta (Vb) repertoire of CD4+ T-cells disclosed a major Vb expansion in all cases: in 9 cases the expanded Vb family was identified (Vb2.1 in 2 cases; Vb3.1 in 2 patients; Vbl3.1 in 4 cases; VblV.l in 1 case); in the remaining 11 patients the expanded Vb family was not identified, indicating that it was not represented in the panel of MoAb used. From the functional point of view, CD4+/NKa+/CD8-/+dim T-cells constantly showed a typical Thl pattern of cytokine production as analyzed after stimulation with PMA+ionomycin at the cytoplasmic level by flow cytometry. In summary, our results indicate that patients with clonal expansions of PB CD4+/NKa+/CD8-/+dim LGL show an indolent disease course; however they frequently have a second neoplasia, the clinical course being usually determined by the associated tumor. Clonal CD4+/NKa+/CD8-/+dim T-cells show a cytotoxic phenotype, a typical Thl pattern of cytokine production and a restricted TCR Vb repertoire with preferential usage of a few Vb families.

Language: English

Type (Professor's evaluation): Scientific