Inability of activated cord blood T lymphocytes to perform Th1-like and Th2-like responses: implications for transplantation.
Cytokines secreted by alloreactive donor T cells play a crucial role in the pathogenesis of both acute and chronic GvHD, a complication of allogeneic hematopoietic transplants that occurs at a lower incidence and severity when human umbilical cord blood (HUCB) is used. Our five-dimensional flow cytometric study performed on 20 HUCB and 20 peripheral blood (PB) samples from healthy adults was focused on the Th1/Th2 cytokine profile of activated HUCB T cells. Lymphocytes of all samples were stimulated by specific mitogens, and cytokine secretion was blocked at the cytoplasmic level. CD4+ and CD8+ cells were then analyzed for surface expression of the very early human activation antigen CD69 and for IFN-gamma and IL-4 intracellular production as expression of Th1-like and Th2-like T cell cytokine response, respectively. HUCB T lymphocytes were shown to be unable to perform both a Th1-like and Th2-like response, as compared with normal PB T cells. However, all lymphocytes from both sources were normally activated, as indicated by regular expression of the CD69 molecule. These data suggest that the low response of HUCB T lymphocytes to mitogens may be responsible for the decreased incidence of acute and chronic GvHD and provide possible explanations for the clinical results in HUCB transplantation.
D'Arena
G
G
Division of Hematology, IRCSS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
Musto
P
P
Cascavilla
N
N
Minervini
M M
MM
Di Giorgio
G
G
Maglione
A
A
Carotenuto
M
M
D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology*; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*