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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Functional aspects of cord blood lymphocytes response to polyclonal and allogeneic activation
A Paiva1, A Freitas, A Loureiro
1Histocompatibility Centre, Coimbra, Portugal.
Insights
Umbilical cord blood (UCB) lymphocytes exhibit distinct phenotypes compared to adult peripheral blood, with altered expression of key immune markers. However, UCB lymphocytes demonstrate normal allogeneic responses and only slightly reduced IFN-gamma production after polyclonal activation.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells.
- Understanding UCB lymphocyte characteristics is crucial for cell-based therapies.
- Phenotypic and functional differences between UCB and peripheral blood lymphocytes are not fully elucidated.
Purpose of the Study:
- To comprehensively characterize the immunophenotype of UCB lymphocytes.
- To evaluate the functional immune responses of UCB lymphocytes.
- To compare UCB lymphocyte characteristics and functions with peripheral blood lymphocytes from healthy donors (PBHD).
Main Methods:
- Extensive immunophenotyping of UCB and PBHD lymphocytes using flow cytometry.
- Assessment of immune response to polyclonal activation (mitogens).
- Evaluation of immune response to allogeneic activation (mixed lymphocyte reaction - MLR, frequency of cytotoxic T lymphocytes - CTL and helper T lymphocytes precursors).
Main Results:
- UCB CD4+ lymphocytes showed increased CD38, CD45RA and decreased CD11a, CD54, HLA-DR.
- UCB CD8+ lymphocytes exhibited increased CD38, CD45RA, CD56 and decreased CD28, CD57, HLA-DR.
- UCB lymphocytes displayed a lower proportion of CD8+ and TCR gamma delta+ cells, and a higher proportion of CD4+ cells.
- Most phenotypic differences between UCB and PBHD lymphocytes diminished after allogeneic stimulation.
- UCB lymphocytes showed normal allogeneic responses and reduced IFN-gamma production upon PHA stimulation.
Conclusions:
- UCB lymphocytes possess distinct phenotypic profiles compared to adult peripheral blood lymphocytes.
- UCB lymphocytes exhibit functional competence, with normal allogeneic responses.
- Slightly diminished IFN-gamma production by UCB lymphocytes warrants further investigation.
Abstract:
With the purpose of contributing to a better knowledge of the phenotypic characteristics and functional activity of umbilical cord blood (UCB) lymphocytes, we have carried out extensive immunophenotyping of these cells, evaluated their immune response to polyclonal and allogeneic activation and then compared these results with those obtained with peripheral blood lymphocytes of healthy donors (PBHD). Our results showed, in CD4+ UCB lymphocytes, an increase of CD38 and CD45RA and a decrease of CD11a (S6F1), CD54 and HLA-DR double positive cells. An increase of CD38, CD45RA and CD56, and a decrease of CD28, CD57 and HLA-DR were observed in CD8+ UCB lymphocytes. Most natural killer UCB cells are CD16+, CD56+, CD57-, and among the UCB cells there is a lower number of CD8+ and TCRgammadelta+ (either CD8- or CD8+), and higher number of CD4+ lymphocytes. After allogeneic stimulus the majority of these phenotypic differences disappeared, which seems to be in agreement with the normal allogeneic response (assessed through MLR, frequency of CTL and helper T lymphocytes precursors) presented by UCB lymphocytes. Regarding the response to polyclonal activation, among the mitogens used, only PHA induced a different result: a lower IFNgamma production by UCB cells.
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