PubMed Health⌕ Search

Biomedical subjects

D Primi

Publications and source records attributed to D Primi.

96 records · Page 6Linked to original sources

Evidence for the existence of self-reactive human B lymphocytes.

Supernatants from human tonsil cells cultured in the presence of the PBAs, LPS and F (ab)2 monomers of rabbit anti-human beta2-microglobulin were found to have a complement-dependent cytotoxic activity to tonsil cells of the same donors. A direct toxic effect of the PBAs on the target cells was excluded by controls. Therefore the most likely explanation for this finding is that human lymphocytes contain a subpopulation of self-reactive B cells which can be triggered by PBAs to release antibodies to self-antigens. The implications of this finding for the understanding of infections accompanied by auto-immune phenomena are discussed.

Antibody Formation↗

Gangliosides, sialoglycoproteins and glucocerebroside in the spleen and bone marrow of patients with beta-thalassemia major.

Bone marrow and spleen samples were studied biochemically to elucidate the nature of the material stored in the large histiocytes present in beta-thalassemic patients. Only the protein-bound N-acetylneuraminic acid (NANA) content of the spleen of homozygous beta-thalassemic patients was significantly higher than that of controls. In the bone marrow, which contained a large number of thalassemic storage cells, the lipid-bound NANA and the glucocerebroside showed a moderate increase, while the amount of protein-bound NANA was much greater than that in controls. These results, in agreement with ultrastructural and histochemical observations, differentiate thalassemic storage cells from other storage cells found in diseases characterized by an increased destruction of blood cells and suggest that there may also be an impairment of the sialoglycoprotein metabolism of the red blood cells in homozygous beta-thalassemia.

Adolescent↗

Assessment of T-cell receptor beta-chain diversity by heteroduplex analysis.

The aim of this work was to search for a simple and alternative approach to the currently used methodologies for the analysis of T-cell receptor repertoire diversity. To this end we studied whether the heteroduplex analysis could be adapted to study the clonality of the T-cell receptor beta chain (TCRBV). We therefore analyzed, by sequencing, the molecular characteristics of the V-D-J junctions of numerous TCRBV chains from a variety of patients and from normal individuals, and compared the results with those obtained with the heteroduplex analysis. The latter procedure involves the amplification of the target TCRBV chains and the denaturation and renaturation of the amplified product to permit the random association of the distinct DNA strands encoding the different junctional regions. Whereas amplified material from polyclonal lymphoid cells migrates on a polyacrylamide gel as a "smear" of bands composed of different-sized polyclonal PCR fragments, the mismatched chains derived from oligoclonal populations migrate as discrete "heteroduplexes" and can be separated from the matched "homoduplex" obtained from homogeneous clonal cells. Our results provide evidence demonstrating that heteroduplex analysis can successfully be applied to the analysis of T-cell clonality in a variety of samples and can be complementary or substitute for the standard approach of TCR cloning and multiple sequencing of junctional regions. Thus, the procedure should facilitate the implementation of the analysis of TCR in diagnostic routine and should find applications in numerous physiologic and pathologic conditions.

Amino Acid Sequence↗

Positive and negative immunoregulation through CD4 depends on the concentration of the specific ligand and on the state of activation of the responding cells.

In order to better define the functional role of the interaction of CD4 polypeptide with the T-cell receptor (TCR) complex, we analysed the effect of an anti-CD4 monoclonal antibody (mAb) on T-cell activation and on the modulation of expression of CD3, CD4 and TCR variable (V) regions. The results presented here demonstrate that both positive and negative modulation of CD3 and TCR V regions can be obtained with different concentrations of the same anti-CD4 mAb and that these effects are functionally directly related to differences in IL2-receptor expression. Moreover, our data show that the dose of anti-CD4 mAb required for modulating CD3- and CD4-molecule expression on activated E+ peripheral blood mononuclear cells is at least 30 times higher than that required to obtain the same effect on resting cells. Thus, our results demonstrate that the interaction of CD4 molecule with its ligand can result in both up and downregulation of TCR and IL2-receptor expression, and that this differential modulation is strictly dependent on the concentration of available ligand as well as on the activation state of the responding cells.

Adult↗