Giulia Casorati

Restriction of the T-cell receptor V delta gene repertoire is due to preferential rearrangement and is independent of antigen selection

To determine whether the limited V gene usage by the T-cell receptor delta (TCRD) chain is dictated by preferential rearrangement or by antigen selection, we characterized and compared the TCRDV gene repertoire of the productive with that of the unprotective allele in 80 human TCRG/TCRD clones. Six different V genes were found on the expressed allele; two of them, provisionally named DV7 and DV8, have not been described before on the surface of TCRG/TCRD T cells. Overall, six V genes and six non-V elements were isolated from the unproductive allele. Interestingly, the same set of genes was rearranged both in the productive and in the unproductive chromosome. These findings seem to suggest that antigen-independent mechanisms play a major role in the restriction of the TCRDV gene repertoire.

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.

Group 1 CD1‐restricted T cells and the pathophysiological implications of self‐lipid antigen recognition

T cell responses are generally regarded as specific for protein-derived peptide antigens. This is based on the molecular paradigm dictated by the T cell receptor (TCR) recognition of peptide-major histocompatibility complexs, which provides the molecular bases of the specificity and restriction of the T cell responses. An increasing number of findings in the last 20 years have challenged this paradigm, by showing the existence of T cells specific for lipid antigens presented by CD1 molecules. CD1-restricted T cells have been proven to be frequent components of the immune system and to recognize exogenous lipids, derived from pathogenic bacteria, as well as cell-endogenous self-lipids. This represents a young and exciting area of research in immunology with intriguing biological bases and a potential direct impact on human health.

Characterization of τ δ TCR in T Cell Clones from Small Intestine of Coeliac Disease Patients

We have isolated T cell lines and clones from jejunal intestinal biopsies and peripheral blood of 7 coeliac disease (CD) patients, and 5 controls. T cells, expanded in the presence of PHA, rhIL-2 and feeder cells, were stained with the following mAbs: TR66 (anti-CD3), BMA032 (anti-αβ TCR), δ1 (anti-δ chain), δTCS1 (anti-Vδ1/Jδ1), BB3 (anti-Vδ2), TiτA (anti-Vτ9), C4-4All (anti-Vτ4), anti-CD4, and anti-CD8. The analysis of T cell lines showed that τ δ+ cells are increased in the gut of CD patients (range 15–52%) when compared to the controls (3–15%). Vδ1 was the most represented Vδ chain (47–76% of total τ δ cells), while Vδ2 was always below 21%. Vδ1 and Vδ2 negative τ δ cells were 11–42%. Vτ9 ranged from 18–68%, while Vτ4 varied between 14 and 41%. On the contrary, gut-τ δ cells derived from controls showed a higher variability in the Vδ and Vτ gene usage.