Death of T cell precursors in the human thymus: a role for CD38.
Thymic T cell maturation depends on interactions between thymocytes and cells of epithelial and hematopoietic lineages that control a selective process whereby developing T cells with inappropriate or self-reactive receptors die. Molecules involved in this process are the TCR expressed on thymocytes together with the CD3 complex and MHC-peptide on accessory cells. However, other molecules may favor or prevent death of thymocytes, thus playing a role in selection. CD38 is expressed by the majority of human thymocytes, mainly at the double-positive (DP) stage. In contrast, CD38 is not found on subcapsular double-negative (DN) thymocytes and on a proportion of medullary single-positive (SP) thymocytes. CD38 enhances death of thymocytes when it is cross-linked by goat anti-mouse (GAM) antiserum or by one of its ligands, CD31, expressed by thymic epithelial cells or transfected into murine fibroblasts (L cells). As most thymocytes are at an intermediate (DP) stage of development, it is likely that these cells are most vulnerable to death mediated via MHC-peptide-TCR interactions that is increased by CD38 cross-linking. DN and SP thymocytes are refractory to CD38-induced apoptosis. Accessory molecules, e.g. CD38, are expressed during thymic cell maturation and their presence is relevant for the survival or death of DP T cells in the course of selection. Based on our data, CD38 enhances thymocyte death by interacting with CD31 expressed by accessory cells. In addition, CD28 expression on developing thymocytes also appears to play a role for their selection and it synergizes with CD38 to induce apoptosis of DP thymocytes.
Tenca
Claudya
C
Section of Human Anatomy, Department of Experimental Medicine, University of Genova, 16132 Genova, Italy.
Merlo
Andrea
A
Zarcone
Daniela
D
Saverino
Daniele
D
Bruno
Silvia
S
De Santanna
Amleto
A
Ramarli
Dunia
D
Fabbi
Marina
M
Pesce
Carlo
C
Deaglio
Silvia
S
Ciccone
Ermanno
E
Malavasi
Fabio
F
Grossi
Carlo E
CE
D036541:ADP-ribosyl Cyclase / Q000276:immunology / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D017209:Apoptosis; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002470:Cell Survival; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins; D051379:Mice; D018448:Models, Immunological; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; C115335:CD3E protein, human; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1