Proliferative and cytotoxic responses of human cord blood T lymphocytes following allogeneic stimulation.
On the basis of the success of recent cord blood transplants, we undertook a comparison of the proliferative and cytotoxic potential, following allogeneic stimulation, of E-rosetted T cells from cord blood or adult peripheral blood (PB3) or bone marrow (BM). The magnitude of the proliferative response of cord blood (CB) T cells to alloantigen was greater than or equal to that of adult PB or BM T cells. Proliferation following culture with IL-2, IL-4, or IL-7 produced a similar result. In contrast, the cytotoxic activity in 1(0), 2(0), or 3(0) mixed leukocyte culture of CB T cells was minimal, typically less than 20% at an effector:target ratio of 100:1. Cytometric analysis of CB T cell populations before and after culture with allostimulation demonstrated similar ratios of CD4+ and CD8+ cells in cultures of CB and adult T cells. Down-regulation of CD45RA antigen expression, a measure of CD4+ cell activation, was comparable in adult and CB cultures. Activation of CD8+ CTL effectors was assessed by the acquisition of CD28 antigen expression. After culture, a smaller proportion of CD8+CD28+ effector cells was present in CB cultures as compared to adult T cell cultures. Thus, following in vitro priming with alloantigen CB T cells generate a vigorous proliferative response yet produce little antigen-specific cytotoxicity. This diminished cytotoxicity may, in part, be related to the low incidence of graft vs host disease thus far noted in human CB transplants.
Risdon
G
G
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121.
Gaddy
J
J
Stehman
F B
FB
Broxmeyer
H E
HE
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000008:administration & dosage; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D007519:Isoantigens; D007371:Interferon-gamma