Lymphocyte subsets and mitogen stimulation of blood lymphocytes in normal pregnancy.
OBJECTIVE
In normal pregnancy the maternal immune system should be directed towards tolerance or suppression in order not to reject the partly foreign feto-placental unit. The aim of this investigation was to find hallmarks of systemic immunosuppression during normal pregnancy.


METHODS
Five healthy primigravidae were examined during pregnancy and postpartum with flow cytometric analysis to define T and B lymphocyte subsets in peripheral blood. In addition, we studied the proliferative response of lymphocytes to mitogens or interleukin-2 (IL-2) alone or in combination with immunomodulating drugs or interleukin-4 (IL-4). The results were compared to healthy, non-pregnant women.


RESULTS
During pregnancy and early puerperium we noted an immune balance in favour of suppression, as measured by increased numbers of T "helper/suppressor" (CD4+CD45RA+) and "suppressor"/effector T cells (CD8+S6F1-), and decreased numbers of T "helper/inducer" (CD4+CD29+), T "helper/memory" (CD4+CD45RO+), killer/effector T cells (CD8+S6F1+), and Natural Killer cells (CD56+), as well as decreased numbers of activated lymphocytes expressing IL-2 receptor (CD25+) and T cells expressing HLA-DR (HLA-DR+CD3+). During pregnancy, lymphocyte proliferation was impaired in autologous serum with concanavalin A (ConA), phytohemagglutinin (PHA), or IL-2. A difference in proliferative response to PHA or IL-2 between cultures with AB serum and autologous serum is suggestive of an immunosuppressor factor in serum during pregnancy. Indomethacin significantly increased lymphocyte proliferation in autologous serum with ConA, indicating PGE2 mediated suppressor activity during pregnancy. Chlorambucil and cimetidine modulated the proliferative response to ConA, indicating an alkylating agent sensitive and a histamine dependent suppressor activity during pregnancy.


CONCLUSIONS
During normal pregnancy, a state of systemic suppression of the maternal immune system seems to be present.
Matthiesen
L
L
Department of Obstetrics and Gynaecology, University Hospital, Linköping, Sweden.
Berg
G
G
Ernerudh
J
J
Håkansson
L
L
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000032:analysis / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology
D007166:Immunosuppressive Agents; D008934:Mitogens