Constitutive expression of the pre-TCR enables development of mature T cells.
Expression and signalling through the pre-TCR and the TCRalphabeta resemble two critical checkpoints during T cell development. We investigated to which extent a pre-TCR can functionally replace mature TCRalpha chains during T cell development. For this purpose, transgenic mice were generated expressing the pre-TCRalpha (pTalpha) under the transcriptional control of TCRbeta regulatory elements. We report here on the interesting finding that constitutive pTalpha expression allows complete T cell maturation. The pre-TCR complex permits a subset of beta-selected thymocytes to mature in the absence of TCRalpha into peripheral T cells (betaT cells) comprising up to 10% of all lymphocytes. Lymphopenia-driven proliferation of these betaT cells is similar to that of conventional alphabetaT cells. Furthermore, betaT cells proliferated and acquired effector function upon stimulation with allogeneic MHC.
Schnell
Silke
S
Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Démollière
Corinne
C
van den Berk
Paul
P
Kirberg
Joerg
J
Jacobs
Heinz
H
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta