Many functional peculiarities of cord blood (CB) lymphocytes and antigen presenting cells, including cytokine production, are associated with low intensity of innate and acquired (cellular and humoral) responses. These peculiarities may have implications both for immunologic maturation in post-natal life and for immune functions after CB transplantation [e.g. the lower incidence of graft-versus-host disease (GvHD) in comparison with after bone marrow transplantation (BMT)]. The aim of our study was to compare the intracellular production of cytokines involved both in phagocyte-dependent immunity/inflammation and in humoral immune responses in CB and adult peripheral blood (PB). DESIGN AND METHODS: Intracellular single cell analysis by flow cytometry was used to detect, following aspecific in vitro stimulation, the production of interferon (IFN)-gamma, Interleukin (IL)-2, IL-1alpha, IL-1beta, IL-8, tumor necrosis factor (TNF)-alpha and -beta, IL-4, IL-5, IL-6, IL-10 and IL-13 by T-cell subsets, NK-cells and monocytes obtained from 10 CB and 10 PB samples. The cytokine production was expressed as the percentage of positive cells. RESULTS: Significantly lower number of CD4+ T-cells producing IFN-g (p<0.001), TNF-alpha (p=0.012) and TNF-beta (p=0.03) and of CD8+ T-cells producing IFN-gamma (p<0.001), IL-2 (p=0.005) and TNF-alpha (p<0.001) were found in CB as compared to PB. In CB we have also found a lower number of NK cells and monocytes producing TNF-alpha (p<0.001 and p=0.001, respectively). In contrast, the number of IL-1alpha+ monocytes was higher in CB than in PB (p=0.03). INTERPRETATION AND CONCLUSIONS: Our data confirm that the cytokines which normally sustain the phagocytic-dependent T helper/cytotoxic 1-type immune responses (IFN-gamma, IL-2 and TNF-alpha) and the NK cell/monocyte-dependent aspecific responses (TNF-alpha) are reduced in CB. Since these cytokines are also involved in acute GvHD pathogenesis, these results are in keeping with the evidence of a low incidence of acute GvHD after CB transplantation.
Intracellular cytokine profile of cord blood T-, and NK cells, and monocytes
KRAMPERA, Mauro;PIZZOLO, Giovanni
2000-01-01
Abstract
Many functional peculiarities of cord blood (CB) lymphocytes and antigen presenting cells, including cytokine production, are associated with low intensity of innate and acquired (cellular and humoral) responses. These peculiarities may have implications both for immunologic maturation in post-natal life and for immune functions after CB transplantation [e.g. the lower incidence of graft-versus-host disease (GvHD) in comparison with after bone marrow transplantation (BMT)]. The aim of our study was to compare the intracellular production of cytokines involved both in phagocyte-dependent immunity/inflammation and in humoral immune responses in CB and adult peripheral blood (PB). DESIGN AND METHODS: Intracellular single cell analysis by flow cytometry was used to detect, following aspecific in vitro stimulation, the production of interferon (IFN)-gamma, Interleukin (IL)-2, IL-1alpha, IL-1beta, IL-8, tumor necrosis factor (TNF)-alpha and -beta, IL-4, IL-5, IL-6, IL-10 and IL-13 by T-cell subsets, NK-cells and monocytes obtained from 10 CB and 10 PB samples. The cytokine production was expressed as the percentage of positive cells. RESULTS: Significantly lower number of CD4+ T-cells producing IFN-g (p<0.001), TNF-alpha (p=0.012) and TNF-beta (p=0.03) and of CD8+ T-cells producing IFN-gamma (p<0.001), IL-2 (p=0.005) and TNF-alpha (p<0.001) were found in CB as compared to PB. In CB we have also found a lower number of NK cells and monocytes producing TNF-alpha (p<0.001 and p=0.001, respectively). In contrast, the number of IL-1alpha+ monocytes was higher in CB than in PB (p=0.03). INTERPRETATION AND CONCLUSIONS: Our data confirm that the cytokines which normally sustain the phagocytic-dependent T helper/cytotoxic 1-type immune responses (IFN-gamma, IL-2 and TNF-alpha) and the NK cell/monocyte-dependent aspecific responses (TNF-alpha) are reduced in CB. Since these cytokines are also involved in acute GvHD pathogenesis, these results are in keeping with the evidence of a low incidence of acute GvHD after CB transplantation.
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