CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection

• Published in: International immunology 1993-09, Vol.5 (9), p.1139-1150
• Main Authors: Yamashita, Iwao, Nagata, Taeko, Tada, Tomio, Nakayama, Toshinori
• Format: Article
• Language: English
• Subjects: activation marker; Animals; Antibodies, Monoclonal; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Biological and medical sciences; Biomarkers; CD4+CD8+ thymocytes; CD4-Positive T-Lymphocytes - immunology; CD69; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunophenotyping; Lectins, C-Type; Lymphocyte Activation - immunology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; positive selection; Receptors, Antigen, T-Cell, alpha-beta - immunology; Spleen - immunology; T cell antigen receptor; T-Lymphocytes, Regulatory - immunology; Thymus Gland - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/5.9.1139

CD69, an ‘activation marker’ that is rapidly induced on mature T cells after stimulation through the T cell antigen receptor (TCR) was found to be expressed on ∼10% of normal thymocytes. All of these CD69+ thymocytes express αβ TCR, and they include both TCRlowCD4+CD8+ and TCRhighCD4+CD8− or CD4−CD8+ thymocytes. The CD69+ cells can be further segregated into heat-stable antigen (HSA)+TCR*HSA−TCRhigh and HSA+TCRhigh thymocyte populations. None of CD69+ cells express the mature T cell marker Qa-2. Thus CD69+ cells present in vivo appear phenotyplcally to represent transitional cell populations between immature TCRlowHSA+Qa-2− double-positive cells and mature TCRhighHSA−QA-2+ single-positive cells. In addition, TCR engagement by MHC molecules is required for CD69 expression in the thymus. Taken together, the CD69 + thymocytes appear to represent the cells auditioning in positive selection process or they are the cells that have been positively selected recently. Analysis of a TCR transgenic mouse model revealed an increased number of CD69+ thymocytes in a positively selecting thymus, whereas no CD69+ transgenic TCR+ thymocytes were observed in the non-selecting thymus. Based on the results of this study, we suggest that the surface expression of CD69 serves as a useful marker to identify and trace those thymocytes that are engaged in the TCR-mediated positive selection process in the thymus.