Accumulation of CTLA-4 expressing T lymphocytes in the germinal centres of human lymphoid tissues

Immunology. 1997 Feb;90(2):265-71. doi: 10.1046/j.1365-2567.1997.00162.x.


CTLA-4, a coreceptor with sequence homology to CD28 is expressed on T cells after activation. Mice deficient for CTLA-4 die young from massive infiltration of many organs by activated T cells, which highlights the essential inhibitory role the coreceptor plays in the regulation of the immune response. To study the prevalence and distribution of CTLA-4 in situ immunohistological analyses were carried out on human tonsils and lymph nodes. Expression of CTLA-4 was restricted to alpha beta T cells, and CTLA-4+ B cells were not observed. In T-cell areas, 2-10% of T cells were positive for CTLA-4 with similar percentages in the CD4+ and CD8+ subpopulations. In the germinal centres (GC) the fraction of CTLA-4+ T cells was much higher (70-90%). This was due to frequent expression of CTLA-4 on the CD4+ helper subpopulation. GC CD8+ T cells were rare and mostly did not express the coreceptor. The CTLA-4+ T-cell fraction was also over-represented among intraepithelial tonsillar T cells. Cycling (Ki-67+) and apoptotic (TUNEL+) T cells were never positive for CTLA-4, while a subset of CD25+ cells did express the coreceptor. Since CTLA-4 is essential for the physiological limitation of the immune response, GC T cells, which are mostly CTLA-4 positive, might be important in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adolescent
  • Adult
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation / analysis*
  • Apoptosis / immunology
  • CTLA-4 Antigen
  • Child
  • Child, Preschool
  • Female
  • Fluorescent Antibody Technique
  • Germinal Center / immunology*
  • Humans
  • Immunoconjugates*
  • Immunoenzyme Techniques
  • Lymph Nodes / immunology*
  • Male
  • Palatine Tonsil / immunology*
  • T-Lymphocyte Subsets / immunology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Abatacept