Immunological studies of human trophoblast: markers, subsets and functions

Abstract

People have many different reasons for wanting to know how the allogeneic relationship in normal human pregnancy is successful, but this question is far from being answered. Meanwhile, investigators will continue to use the ideas, approaches and tools with which they have experience and in which they have placed their confidence. Some study the factors which regulate immune functions in the fetus (for review see Murgita & Wigzel 1981); other focus more on the mother (for review see Rocklin et al. 1979); while yet others examine specialized aspects of abnormal pregnancies such as spontaneous abortion (Gill 1983). Although no one knows how the system operates to favor pregnancy, our particular bias is that trophoblast is the driving force which makes it work; for, without trophoblast, there is no pregnancy. This prejudice grew from our early observations of immunopathology in normal placentae (McCormick et al. 1971, Faulk et al. 1974, Faulk et al. 1980b, and reviewed by Faulk & Fox 1982) and was extended and amplified by experiments which showed that trophoblast, as well as antibodies to trophoblast, were able to impede allogeneic recognition as measured by specific inhibition of the mixed lymphocyte culture reaction (McIntyre & Faulk 1979 & 1979a). For a variety of reasons, many laboratories became interested in trophoblast-antigen biochemistry, and a burst of publications appeared on this subject (Faulk et al. 1977, Whyte & Loke 1979, Ogbimi et al. 1979, see review by Johnson et al. 1980). Some of this work confirmed and extended an earlier hypothesis from our laboratory that trophoblast membranes could serve as a hapten-carrier system where one group of trophoblast antigens (TA1) was the carrier, and a second group (TA2) was the hapten (Faulk et al. 1978). This hypothesis invoked a concept of trophoblast-lymphocyte cross-reactive antigens, an idea which was subsequently confirmed biochemically by showing human placental cell-surface antigens on peripheral blood lymphocytes (Hamilton et al. 1980). McIntyre and Faulk (1982, 1982a) later showed that these antigens were allotypic, and data have been provided in the above paragraphs to show that these components of trophoblast membranes are capable of serving as immunogens to stimulate the mother to mount immune recognition of her blastocyst. Indeed, it is presently our interpretation that successful nidation depends upon maternal recognition of the blastocyst, and that a lack of recognition results in spontaneous abortion, sometimes occurring so early that the mother is not aware that she was pregnant (Miller et al. 1980).(ABSTRACT TRUNCATED AT 400 WORDS)