Expression of cell interaction molecules by immature rat thymocytes during passage through the CD4+8+ compartment: developmental regulation and induction by T cell receptor engagement of CD2, CD5, CD28, CD11a, CD44 and CD53.
Rat thymocytes of the T cell receptorlow (TcRlow) CD4+8+ subset which is the target of repertoire selection are heterogeneous with respect to expression of the cell interaction (CI) molecules CD2, CD5, CD11a/CD18 (LFA-1), CD28 and CD44. We show that this heterogeneity is due to the developmental regulation of these CI molecules during passage through the CD4+8+ compartment, and to up-regulation by TcR engagement. Thus, cohorts of CD4+8+ cells differentiating synchronously in vitro from their direct precursors, the immature CD4-8+ cells, were homogeneous with regard to CI molecule expression. Upon entry into the CD4+8+ compartment, they expressed relatively high levels of CD2 and CD44, and moderate levels of CD5, CD28 and CD11a. CD2, CD28 and CD44 were slightly down-regulated during the following 2 days, whereas CD5 slightly increased and CD11a remained constant. TcR stimulation using immobilized monoclonal antibodies resulted in rapid and dramatic up-regulation of CD2, CD5 and CD28 and, to a lesser extent, of CD11a and CD44. Finally CD53, a triggering structure absent from unstimulated CD4+8+ thymocytes was also rapidly induced by TcR stimulation. Inclusion of interleukin (IL)-2, IL-4, or IL-7 in this in vitro differentiation system did not affect the levels of CI molecules studied. Since the high levels of CI molecules induced by TcR-stimulation correspond to those found in vivo on TcRintermediate thymocytes known to be undergoing repertoire selection, these results suggest that upregulation of CI molecules by TcR engagement provides a mechanism by which thymocytes that have entered the selection process gain preferential access to further interactions with stromal and lymphoid cells in the thymus.
Mitnacht
R
R
Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
Tacke
M
M
Hünig
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018845:CD11 Antigens / Q000032:analysis; D018801:CD2 Antigens / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D018956:CD5 Antigens; D016827:CD8 Antigens / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D018960:Hyaluronan Receptors; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D060265:Tetraspanin 25
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018801:CD2 Antigens; D018106:CD28 Antigens; D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D002352:Carrier Proteins; C554896:Cd53 protein, rat; D018960:Hyaluronan Receptors; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D060265:Tetraspanin 25