The human thymic microenvironment: an immunohistologic study.

The human thymic microenvironment has been analyzed in the fetal and child thymus (from 14th gestational week onwards) with immunohistologic methods by using combinations of antisera on cells in suspension and on cell aggregates as well as in tissue sections of frozen or formalin-fixed samples. In the child thymus cortical thymocytes express a nuclear enzyme, terminal deoxynucle-otidyl transferase (TdT), as well as a cortical thymocyte specific antigen (HTA-1) and other thymocyte/T cell antigens (HuTLA), but no detectable HLA-D (la-like, p28,33) and HLA-A,B,C antigens. These cortical thymocytes form close cell-cell contacts with a network of epithelial cells which, in contrast to thymocytes, express large amounts of la-like and moderate amounts of HLA-A,B,C antigens. This arrangement may ensure that efficient epithelial-thymocyte interactions take place and that TdT, a possible ‘somatic mutagen’, acts in a strictly HLA controlled microenvironment. In the thymic medulla >95% of lymphoid cells are TdT,HTA-1-, HuTLA+,HLA-A,B,C+,Ia-, and only 3 to 5% cells show the TdT+,HTA-l+ phenotype (migrants from the cortex?). The medullary stromal cells are abundant and show strong staining for la-like antigens and HLA-A,B,C These cells include interdigitating reticular (IDR) cells that may belong (or be closely related) to a population of brilliantly la-positive circulating “veiled” cells in the interlobular thymic septae and in the peripheral lymph, and to the IDR cells observed in the T-dependent regions of lymph nodes and spleen. In the fetal thymus large lymphoid cells (putative pro-thymoeytes) are present; these blasts as well as the vast majority of fetal HTA-1+ (cortical) thymocytes fail to express detectable amount of TdT. During ontogeny TdT seems to be first generated within the thymus in a subset of small IITA-1+ cells. HLA expression on stromal cells (and the lack of it on cortical thymocytes) is nevertheless similar in fetal and infant thymus, which again points to the probable physiologic importance of this peculiar thymic microenvironment.