IS CORPUS-LUTEUM REGRESSION AN IMMUNE-MEDIATED EVENT - LOCALIZATION OF IMMUNE-SYSTEM COMPONENTS AND LUTEINIZING-HORMONE RECEPTOR IN HUMAN CORPORA-LUTEA

Factors determining the life span of the human corpus luteum (CL) are not known. In addition to being determined by hormonal factors, such a s hCG, the life of luteal cells may be determined by the preservation of luteal vascularization. Furthermore, the CL represents an immunolog ically unique tissue, as it is formed after menarche, long after adapt ation of the immune system toward self. Thus, CL regression may be imm unologically mediated. To determine what role the vasculature and immu ne system play in human CL development and regression, we examined imm unohistochemically 1) the expression of Thy-1 differentiation protein by vascular pericytes, 2) the expression of major histocompatibility c omplex (MHC) class I and class II molecules in granulosa lutein cells (GLC), and 3) infiltration of the CL by macrophages and T lymphocytes, LH receptor (LHR) and cytokeratin 18 expression were also studied. In developing CL, the pericytes of luteal microvasculature released Thy- 1 differentiation protein among the endothelial cells of proliferating vessels, In mature CL, Thy-1 released from vascular pericytes accumul ated on the surface of GLC, and these cells exhibited LHR immunoreacti vity (LHRI). Overall LHRI increased during the luteal phase and was st rongest at the beginning of the late luteal phase. Although vascular p ericytes showed strong LHRI, no staining of endothelium was detected d uring the luteal phase. GLC exhibited strong cytokeratin staining and moderate staining for MHC class 1 and MHC class II antigens; numerous macrophages were detected in luteal tissue. During pregnancy, the stai ning pattern was similar to that seen in the mature CL at the end of t he midluteal phase. During the late luteal phase, surface expression o f MHC class I and MHC class II antigens by GLC was substantially enhan ced, and some T cells invaded among luteal cells. By the end of the cy cle, an acute regression of vasculature and luteal tissue was observed along the fibrous septa. The remaining GLC showed only surface and no cytoplasmic LHRI. During the subsequent cycle, in the presence of num erous T cells, regressing GLC exhibited strong surface expression of v arious macrophage markers, such as CD4, CD14, CD68, and leukocyte comm on antigen, a feature not detected in the CL during the luteal phase n or described in other tissues. A complete loss of cytokeratin staining in GLC was observed. In regressing CL, strong LHRI was present in the endothelium of small and large luteal vessels. In conclusion, vascula r pericytes and macrophages may stimulate the development and senescen ce of luteal tissue. The senescence of GLC may be inconsistent with pr eservation of luteal vasculature, and T lymphocytes appear to particip ate in terminal regression of the CL. Regression of luteal tissue ther efore resembles immunologic rejection of a transplant. During pregnanc y, the aging process of GLC appears to be interrupted, possibly due to the temporary acceptance of the CL ''graft.''