Clonally expanded CD3+, CD4-, CD8- cells bearing the α β or the γ δ T-cell receptor in patients with the lymphoproliferative disease of granular lymphocytes

Abstract Among 60 retrospectively assessed patients with the lymphoproliferative disease of granular lymphocytes (LDGL), lymphocytes from only 2 patients had the CD3+, CD4−, CD8− phenotype, rarely observed in normal peripheral blood lymphocytes (about 3%). In this paper we report a detailed study of lymphocytes isolated from these two patients. The cells from patients 1 had the CD3+, CD4−, CD8−, WT31−, βF1−, TCRδ1+, TiγA−, BB3+, CD7+, CD16−, CD57+ phenotype, while cells from patient 2 had a phenotype even more rarely observed on normal lymphocytes: CD3+, CD4−, CD8−, WT31+, βF1+, TCRδ1−, CD7+, CD16−, CD57+. Thus, in only the first case the cells expressed the γ δ T-cell receptor (TCR) on the membrane, while the cells from the second case had the α β TCR. Genetic studies showed that in case 1 the TCR γ gene was rearranged and the β chain gene configuration was germline; the TCR mRNA was of normal size for the γ chain, while that of the β chain was truncated. Case 2 had the β and the γ genes of the TCR rearranged, but only the α and β mRNA were expressed. In agreement with these findings, the δ chain gene of the TCR was rearranged in case 1 and was deleted in case 2. Cytotoxic activity was absent in cells from case 1 and low in case 2; in the latter, the lytic activity could be up-regulated following incubation with IL-2 or an anti-CD3 monoclonal antibody. Our study indicates that CD3+, CD4−, CD8− lymphocytes are rarely expanded in patients with LDGL. The detection of a lymphoproliferative disease of a CD3+, CD4−, CD8−, α β+ cell may contribute to a better characterization of this novel lymphocytic subpopulation.