ONTOGENY OF HUMAN-LYMPHOCYTES DURING INTRAUTERINE LIFE .1. PHENOTYPICAL ANALYSIS OF T-CELLS

In humans the fetal lymphoid system develops in an environment virtual ly free of ''non-self'' antigens and undergoes two basic phenomena, (a ) membrane expression of antigen-specific receptors and other surface molecules, (b) induction of tolerance towards ''self'' antigens. To ex amine fenotypical and functional properties of human lymphocytes at ve ry early stages of development, we have analyzed circulating T lymphoc ytes in fetuses at the second trimester of pregnancy and in full-term newborns, by using monoclonal antibodies specific for leukocyte antige ns, immunofluorescence techniques and flow cytometry. In blood samples from both fetuses and newborns, approximately 60% of mononucleare cel ls express the CD7, CD2, CD3 and CD5 molecules, while 5% only of cells are positive for CD1. Distinct subsets of T cells bear the CD4 and CD 8 molecules, with a few cells (less than 5%) coexpressing the two mole cules. In fetuses, roughly 95% of CD7 or CD3 cells are positive for th e CD38 and CD28 molecules; looking at the TCR receptor, the alfa/beta type is expressed by 90% of T cells, with less than 5% of cells expres sing the gamma/delta TCR. In fetuses 69% of T cells are CD45RA(+), and 11% CD45RO(+). This observation implies that approximately 15% of T c ells do not express either the RA or RO isoforms of the CD45 leukocyte antigens. Eleven % of fetal T cells are CD25(+), while less than 2% e xpress HLA-DR antigens. The main and significant changes observed in n ewborns Versus fetuses are the lower percentages of CD1(+) and CD4(+)C D8(+) of lymphocytes. Furthermore, compared to the values observed in fetuses, higher percentages of newborns' CD3(+) lymphocytes express th e alfa/beta TCR (94 vs. 88%) and the RA isoform of CD45 (85 vs. 69). T he presented data provide reference values for the normal development of the human immune system during the intrauterine life and might be u seful for prenatal diagnosis of congenital immunodeficiencies. Even if functional studies are clearly needed, we hypothesize that high level expression of some surface molecules such as CD28 or CD38 during the intrauterine life might be related to the easy induction of tolerance at this stage of development.