Accumulation of CTLA‐4 expressing T lymphocytes in the germinal centres of human lymphoid tissues‘pa

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 αβ 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.