Table Of ContentCurren t Topics in
Microbiology
222 and Immunology
Editors
R.W. Compans, Atlanta/Georgia
M. Cooper, Birmingham/Alabama· J.H. Hogle,
Boston/Massachusetts· H. Koprowski,
Philadelphia/Pennsylvania . F. Me1chers, Basel
M. Oldstone, La Jolla/California· S. Olsnes, Oslo
M. Potter, Bethesda/Maryland· H. Saedler, Cologne
P.K. Vogt, La Jolla/California· H. Wagner, Munich
Springer
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Reproductive
Immunology
Edited by L.B. Olding
With 17 Figures and 10 Tables
, Springer
Professor LARS B. OLDING, M.D., Ph.D.
Department of Immunology, Microbiology,
Pathology and Infectious Diseases
Karolinska Institute
Division of Pathology, F42
Huddinge University Hospital
S-141 86 Huddinge
Sweden
Cover illustration: "The human fetus in the uterus". Pencil-drawing
by Leonardo Da Vinci around 1510. Royal Library, Windsor
Castle.
Cover design: Design & Production GmbH, Heidelberg
ISSN 0070-217X
ISBN-13: 978-3.Q42-64475-7 e-ISBN-13: 978-3.Q42-606144
DOl: IO.lOO7/978-3.Q42-606144
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Foreword
Discrimination of self from nonself is the major function of the
immune system and understanding the mechanism(s) involved a
main employer of immunologists. Hence, the age-old puzzle of
why a fetus that contains a panel of major histocompatibility
(MHC) antigens derived from its mother and its father is not
rejected (spontaneously aborted) by lymphocytes from its mother
who should theoretically recognize foreign MHC molecules from
the father has remained of great interest. This dilemma has enticed
immunologists and developmental biologists for many years.
This volume was created to present the information currently
on hand in this subject to the scientific public. The guest editor,
Professor Lars Olding, has a long and distinguished history of
contributions in this field, having been one of the main propo
nents of the argument that lymphocytes from the fetus play an
active role in this process by suppressing lymphocytes from the
mother from proliferating and thereby acting as killer cells. His
work has defined the phenomenon and identified suppressor
molecules (factors) involved in the process. In a different but
related chapter, Margareta Unander extends such observations to
the clinical study of women with repeated "habitual" mIS
carriages.
But, in addition, there is the topography associated with
maternal-fetal lymphoid cell interactions. Knowledge of the
structural basis of the human placenta, and the immunobiology
of the decidua and of trophoblasts are important issues for sol
ving the puzzle. Information in these areas is supplied by several
experts who have contributions in this line of research including
Drs. Faulk, Clark, and Redline. To round out this volume, other
contributors (Drs. Adinolfi, Chaouat, Menu, Papadogiannakis,
Goldman, and Goldblum) discuss trafficking of leukocytes, other
issues of T-cell reactivity in the fetus, newborn or mother, and
antigen presentation in specialized cells at the maternal-fetal in
terface.
The lessons to be learned from study of the immunobiology
of maternal-fetal interactions are not only important for the area
VI Foreword
of normal birth and spontaneous miscarriages, but have the po
tential to provide both understanding and development of
pharmacological approaches to enhance successful transplanta
tion and gene therapy.
La Jolla, California MICHAEL B.A. OLDSTONE
Preface
Reproductive immunology encompasses virtually all facets of
modern immunobiology; accordingly, a complete review would
be encyclopedic. Therefore, this volume includes only selected
topics in recent research, older investigations of relevance, and
topics which have been to some extent ignored by the inter
national community of scientists in the field.
Recent progress in immunogenetics that sheds light on the
major histocompatibility complex (MHC) antigens on tropho
blasts, particularly the unique HLA-G antigen on invading
"frontier" trophoblasts, is reviewed by Drs. Ober and van der
Ven. They also elucidate the old and controversial question of
whether parental sharing of one or more HLA antigen compro
mises gestation, a subject that has been studied in a secluded
religious sect. Modern aspects of the human placental structure
associated with strictly defined immune cells are then reviewed by
Dr. Redline. Next, the decidua and its occupancy by bone-mar
row-derived cells with strong immunological potency are thor
oughly discussed by Drs. Arck and Clark. Immunomodulation of
these cells is crucial for successful implantation of the blastocyst.
The important problem of the ontogeny, differentiation, and
maturation of fetal immunity is discussed at length by Dr. Adi
nolfi in terms of both the natural and. acquired states. Drs
Chaouat and Menu subsequently provide an overview of ma
ternal T-cell reactivity, which is important for the recognition of
fetal antigens, as shown in vitro and in animal experiments. The
ability of the trophoblast to evade recognition, destruction, and
rejection by maternal cytotoxic immune cells is the topic reviewed
by Drs. Torrey, McIntyre, and Faulk. They propose that pro
tection might be delivered by "blocking antibody" raised against
an antigen common to both trophoblasts and lymphocytes. This
observation, although controversial, has attracted great interest.
The extent and possible importance of leakage of fetal leukocytes
into the maternal circulation within the placenta - and perhaps in
the opposite direction as well - is the controversial issue detailed
in the chapter by Dr. Papadogiannakis. The importance of
VIn Preface
nonspecific suppressor-T-cell actlVlty in cord blood, pros
taglandins, and alpha-fetoproteins in modulating maternal-fetal
immune reactions is the subject of a chapter written by Drs.
Olding, Papadogiannakis, Barbieri, and Murgita. New aspects of
functional suppressor cells and of the genuine immunomodu
latory potency of prostaglandins and alpha-fetoproteins are em
phasized.
Despite the mass of new information on reproductive im
munobiology during the last three decades, few clinical applica
tions have emerged. The difficulty in extrapolating results from
experiments with animals or from in vitro investigations to the
conditions of human pregnancy is obvious. Rarely can one study
immunological events in vivo at the maternal-fetal interface in
the human placenta, and laboratory animals differ too greatly in
structure and function from humans for ready application of
research outcomes. However, one clinical application is reviewed
here by Dr. Unander: the treatment of women who have normal
fertility but repeatedly undergo spontaneous (chronic or "habi
tual") abortions, with leukocyte transfusions that produce the
missing blocking antibodies. This kind of treatment is the subject
of much controversy, but can apparently be successful. It is a
well-known phenomenon that mothers continue to protect their
babies after birth by means of antibodies transferred in breast
milk. Less well known is that maternal immune cells in this milk
might actually penetrate the barrier of the newborn's gut, as re
viewed by Drs. Goldman and Goldblume in the chapter that
concludes this volume.
I am indebted to the authors for their great efforts in pre
paring their reviews and to the publishers for their kind co
operation and skill.
Stockholm, April 1997 LARS B. OLDING
List of Contents
e. OBER and K. VAN DER VEN
Immunogenetics of Reproduction: An Overview
R.W. REDLINE
The Structural Basis of Maternal-Fetal Immune
Interactions in the Human Placenta 25
P.e. ARCK and D.A. CLARK
Immunobiology of the Decidua. . . . . . . . . . . . . . . . . . . 45
M. ADINOLFI
Ontogeny of Human Natural and Acquired Immunity 67
G. CHAOUAT and E. MENU
Maternal T Cell Reactivity in Pregnancy? 103
D.S. TORRY, 1.A. McINTYRE, and W.P. FAULK
Immunobiology of the Trophoblast: Mechanisms
by Which Placental Tissues
Evade Maternal Recognition and Rejection. . . . . . . . .. 127
N. PAPADOGIANNAKIS
Traffic of Leukocytes Through the Maternofetal
Placental Interface and Its Possible Consequences 141
L.B. OLDING, N. PAPADOGIANNAKIS, B. BARBIERI,
and R.A. MURGITA
Suppressive Cellular and Molecular Activities
in Maternofetal Immune Interactions;
Suppressor Cell Activity, Prostaglandins,
and Alpha-Fetoproteins . . . . . . . . . . . . . . . . . . . . . . .. 159
A.M. UNANDER
The Immunopathology of Recurrent Abortion. . . . . . .. 189
A.S. GOLDMAN and R.M. GOLDBLUM
Transfer of Maternal Leukocytes to the Infant
by Human Milk ............................. 205
Subject Index ............................... 215
List of Contributors
(Their addresses can be found at the beginning of their respective
chapters.)
ADINOLFI, M. 67 MENU, E. 103
ARCK, P.e. 45 MURGITA, R.A. 159
BARBIERI, B. 159 OBER, e. 1
CHAOUAT, G. 103 OLDING, L.B. 159
CLARK, D.A. 45 PAPADOGIANNAKIS, N. 141,159
FAULK, W.P. 127 REDLINE, R.W. 25
GOLDBLUM, R.M. 205 TORRY, D.S. 127
GOLDMAN, A.S. 205 UNANDER, A.M. 189
McINTYRE, ] .A. 127 VAN DER VEN, K.
