A human homeobox gene, HB24, inhibits development of CD4+ T cells and impairs thymic involution in transgenic mice.
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.
Deguchi
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Y
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Agus
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Kehrl
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JH
D000818:Animals; D000906:Antibodies / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000032:analysis*; D004247:DNA / Q000302:isolation & purification; D015342:DNA Probes; D018819:Dipeptidyl Peptidase 4; D004797:Enzyme-Linked Immunosorbent Assay; D005801:Genes, Homeobox; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D012016:Reference Values; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000502:physiology*
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D015342:DNA Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA; D018819:Dipeptidyl Peptidase 4