T cells from newborn humans are fully capable of developing into cytotoxic T lymphocyte effector cells in adoptive hosts.
BACKGROUND
The finding of reduced incidence of graft-versus-host disease (GVHD) associated with cord blood transplantation, compared to unrelated allogeneic bone marrow, could be related to the lower number of T cells infused in the cord blood (CB) inoculum or it might represent an intrinsic property of CB T cells. We investigated the in vivo function of human cord blood mononuclear cells (CBMC) after their adoptive transfer into lethally irradiated BALB/c radioprotected with severe combined immunodeficiency (SCID) mouse bone marrow.


METHODS
The ability of human CBMC to engraft and produce antigen-specific alloreactive cytotoxic T lymphocytes (CTLs) and antibodies was determined by FACS, 51Chromium-release assay, and ELISA.


RESULTS
Recipients of human CBMC showed engraftment of high levels of both CD14+ and CD3+ cells. Human cells recovered from the peritoneal cavity of chimeric mice, 1 week after immunization with irradiated allogeneic cells, showed adult-level human CTL response against the immunizing cells, without further stimulation in vitro. In contrast, immunization with the tetanus (TT) antigen did not lead to the generation of anti-TT immunoglobulins (Ig) in the cord blood chimera. Furthermore, whereas the addition of purified adult T cells to the cord blood inoculum resulted in the enhancement of human Ig production of both IgG and IgM subclasses, it could not induce antigen-specific antibodies after immunization.


CONCLUSIONS
This report demonstrates in mice for the first time the generation of classical human alloreactive CTLs, derived from cord blood cells. The alloreactivity exhibited by the cord blood mononuclear cells is not different from that displayed by cells originating from adult blood. Any reduction in the observed GVHD associated with cord blood transplants might therefore represent a quantitative difference in the total number of T cells infused.
Marcus
Hadar
H
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Dekel
Benjamin
B
Arditti
Fabian D
FD
Reich-Zeliger
Shlomit
S
Segal
Harry
H
Bocher
Wulf O
WO
Reisner
Yair
Y
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D002678:Chimera; D005312:Fetal Blood / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology