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Mixed lymphocyte culture of human fetal liver cells
B Lindton1, L Markling, O Ringdén
1Department of Obstetrics and Gynecology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Insights
The human fetus can mount an immune response as early as 11-12 weeks of gestation, challenging previous timelines. This early fetal immune competence may impact in utero transplantation success.
Area of Science:
- Immunology
- Developmental Biology
- Fetal Medicine
Background:
- The immunological capabilities of the human fetus during early gestation remain incompletely understood.
- Mixed lymphocyte culture (MLC) is a key functional assay for assessing immune responses to foreign antigens.
Purpose of the Study:
- To investigate the immunological function of the human fetus in the first and second trimesters.
- To determine the earliest gestational age at which fetal cells exhibit immunocompetence.
Main Methods:
- Human fetal liver and thymic tissues were sourced from gestational weeks 7-17.5.
- One-way mixed lymphocyte culture (MLC) was performed on cells from 47 fetuses.
- Fetal cells were stimulated with irradiated fetal liver cells, adult bone marrow, and peripheral blood lymphocytes.
- Immune activity was quantified by measuring radiolabeled thymidine incorporation into DNA.
Main Results:
- The human fetus demonstrates immunocompetence by 11-12 weeks of gestation, with some evidence of reactivity even earlier.
- Immune responses in very immature fetal livers (less than 8 weeks gestation) appeared to be inhibited.
Conclusions:
- Fetal immune systems can react to foreign transplantation antigens earlier than previously reported.
- The onset of fetal immune reactivity varies significantly between individuals.
- These findings may offer insights into the limited success rates of in utero hematopoietic stem cell transplantation.
Objective:
In order to study the immunological function of the human fetus in the first and second trimesters, mixed lymphocyte culture (MLC) of fetal liver and thymic cells was performed. MLC is a functional test to determine human lymphocyte antigen-D incompatibilities.
Methods:
Human fetal liver and thymic tissue was obtained from abortions in gestational weeks 7-17.5. Forty-seven fetuses were studied with one-way MLC. The cells were stimulated by adding irradiated fetal liver cells, adult bone marrow and peripheral blood lymphocytes. The activity was measured as DNA incorporation of radiolabeled thymidine.
Results:
The results indicate that the human fetus is competent to react as early as 11-12 weeks of gestation and in some cases even earlier. In very immature fetal livers (< 8 weeks), the MLC seems to be inhibited.
Conclusions:
Our data suggest that the human fetus can react against foreign transplantation antigens earlier than previous papers have claimed. The onset of reactivity seems to differ considerably among fetuses. The present findings may explain some of the limited success of in utero transplantations of hematopoietic stem cells in human fetuses of normal immunological status.