A human homeobox gene, HB24, inhibits development of CD4+ T cells and impairs thymic involution in transgenic mice

• Published in: The Journal of biological chemistry Vol. 268; no. 5; pp. 3646 - 3653
• Main Authors: DEGUCHI, Y, AGUS, D, KEHRL, J. H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.02.1993
• Subjects: Animals; Antibodies - blood; Antigens, Differentiation, T-Lymphocyte - analysis; Biological and medical sciences; Blotting, Southern; CD4 Antigens - analysis; Dipeptidyl Peptidase 4; DNA - isolation & purification; DNA Probes; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Homeobox; Hematopoietic Stem Cells - physiology; Humans; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - analysis; Reference Values; Restriction Mapping; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; Thymus Gland - immunology; Thymus Gland - pathology; Thymus Gland - physiology; Human; Gene; Thymocyte; T-Lymphocyte; Transgenic animal; Activation; Cell differentiation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)53742-X

The HB24 gene encodes a diverged human homeodomain-containing protein known to be expressed in hematopoietic progenitors and activated lymphocytes. We have generated transgenic mice that express HB24 under the control of the T cell receptor beta chain promoter/enhancer. Analysis of T cells and thymocytes from the transgenic mice revealed a marked increase in activated cells as assessed by cell size profiles and interleukin-2 receptor expression. Within the thymus these changes were most pronounced in the CD4+CD8- subset. Strikingly, the normal development of CD4+ T cells in the transgenic mice was impaired. Single positive CD4 cells were reduced 35% in the thymus, and CD4+ T cells were reduced 90% in the spleen and lymph nodes compared to the controls. Similar findings were found both in young mice (6 weeks old) and in more elderly mice (1 y old). However, the thymuses of the elderly mice failed to undergo normal involution. Sera from HB24 transgenic mice had levels of IgG1 10-100-fold lower than sera from matched controls, most likely as a consequence of the decrease in CD4+ T cells. These transgenic mice provide a useful model for studying the role of HB24 in lymphocyte activation as well as for understanding the effects of abnormal T cell activation on thymic and T cell development.