A HUMAN HOMEOBOX GENE, HB24, INHIBITS DEVELOPMENT OF CD4+ T-CELLS AND IMPAIRS THYMIC INVOLUTION IN TRANSGENIC MICE

被引:0
|
作者
DEGUCHI, Y
AGUS, D
KEHRL, JH
机构
[1] NIAID, IMMUNOREGULAT LAB, BLDG 10, RM 11B-13, BETHESDA, MD 20892 USA
[2] NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA
关键词
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3646 / 3653
页数:8
相关论文
共 50 条
  • [31] Imiquimod-induced dermatitis impairs thymic tolerance of autoreactive CD4+ T cells to desmoglein 3
    Iriki, Hisato
    Mukai, Miho
    Ito, Hiromi
    Kurebayashi, Yutaka
    Amagai, Masayuki
    Takahashi, Hayato
    JOURNAL OF DERMATOLOGICAL SCIENCE, 2020, 100 (03) : 166 - 174
  • [32] CD4+ AND CD8+ T-CELLS ACQUIRE SPECIFIC LYMPHOKINE SECRETION POTENTIALS DURING THYMIC MATURATION
    BENDELAC, A
    SCHWARTZ, RH
    NATURE, 1991, 353 (6339) : 68 - 71
  • [33] Specific ablation of CD4+ T-cells promotes heart regeneration in juvenile mice
    Li, Jiatao
    Liang, Cai
    Yang, Kevin Y.
    Huang, Xiuzhen
    Han, Mao Ying
    Li, Xisheng
    Chan, Vicken W.
    Chan, Kathleen S.
    Liu, Di
    Huang, Zhan-Peng
    Zhou, Bin
    Lui, Kathy O.
    THERANOSTICS, 2020, 10 (18): : 8018 - 8035
  • [34] RAPID LOSS OF CD4+ T-CELLS IN HUMAN-PBL-SCID MICE BY NONCYTOPATHIC HIV ISOLATES
    MOSIER, DE
    GULIZIA, RJ
    MACISAAC, PD
    TORBETT, BE
    LEVY, JA
    SCIENCE, 1993, 260 (5108) : 689 - 692
  • [35] DEPLETION OF EITHER CD4+ OR CD8+ T-CELLS ACCELERATES THE DEVELOPMENT OF SPONTANEOUS MYOSITIS IN SJL/J MICE
    WELLER, AH
    PONZIO, NM
    FASEB JOURNAL, 1995, 9 (03): : A526 - A526
  • [36] HUMAN CD4+ CYTOLYTIC T-CELLS KILL ANTIGEN-PULSED TARGET T-CELLS BY INDUCTION OF APOPTOSIS
    RAHELU, M
    WILLIAMS, GT
    KUMARARATNE, DS
    EATON, GC
    GASTON, JSH
    JOURNAL OF IMMUNOLOGY, 1993, 150 (11): : 4856 - 4866
  • [37] Absence of CD4+ T cells impairs host defence of mice infected with Fonsecaea pedrosoi
    Teixeira de Sousa, M. da Gloria
    Ghosn, E. E. B.
    Almeida, S. R.
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2006, 64 (06) : 595 - 600
  • [38] DEVELOPMENT AND FUNCTION OF T-CELLS IN MICE WITH A DISRUPTED CD2 GENE
    KILLEEN, N
    STUART, SG
    LITTMAN, DR
    EMBO JOURNAL, 1992, 11 (12): : 4329 - 4336
  • [39] LISTERIA-INDUCED TH1 DEVELOPMENT IN ALPHA-BETA-TCR TRANSGENIC CD4+ T-CELLS
    HSIEH, CS
    MACATONIA, SE
    TRIPP, CS
    WOLF, SF
    OGARRA, A
    MURPHY, KM
    JOURNAL OF IMMUNOLOGY, 1993, 150 (08): : A3 - A3
  • [40] PREDOMINANCE OF MEMORY T-CELLS (CD4+, CDW29+) OVER NAIVE T-CELLS (CD4+, CD45R+) IN BOTH NORMAL AND DISEASED HUMAN-SKIN
    BOS, JD
    HAGENAARS, C
    DAS, PK
    KRIEG, SR
    VOORN, WJ
    KAPSENBERG, ML
    ARCHIVES OF DERMATOLOGICAL RESEARCH, 1989, 281 (01) : 24 - 30