BACKGROUND: Cord blood (CB) transplants have a significantly lower incidence of graft-versus-host disease (GVHD) compared to marrow or peripheral blood transplants. Because antigen-presenting cells and regulatory T cells (Treg) are involved in transplant tolerance, this study was aimed at analyzing the distribution of dendritic cells (DCs) and CD14+ monocyte-specific subsets in CB and adult peripheral blood (APB) and comparing the ability of DCs from these two blood sources to induce CD4+ Treg. STUDY DESIGN AND METHODS: Myeloid DCs (mDCs), plasmacytoid DCs, the CD14+ cell subsets CD14+CD16+ and CD14+CD209+, and CD4+ T cells were analyzed by fluorescence-activated cell sorting (FACS) in whole blood. To evaluate the functionality of DCs, isolated CD3+ T cells from an adult donor were cultured with allogenic DC-enriched fraction from CB or APB, and CD4+ Treg generation was determined by FACS. Additionally, tumor necrosis factor (TNF)-alpha and interferon (IFN)-alpha release by DCs was measured. RESULTS: CB had a lesser frequency of DCs and specific CD14+ monocyte subsets than APB. After stimulation, monocytes from CB secreted less TNF-alpha than those from APB. Moreover, DCs from CB exhibited a more immature phenotype and had a decreased capacity to release TNF-alpha and IFN-alpha than those derived from APB, but on the contrary, they were efficient inducers of CD4+ T cells with a phenotype of Treg. CONCLUSION: The tolerogenic immunophenotype and diminished functionality of CB DCs can be important to create a microenvironment where Treg develop, that in turn may be relevant to observed lower incidence of chronic GVHD after CB transplantation.
BACKGROUND: Cord blood (CB) transplants have a significantly lower incidence of graft-versus-host disease (GVHD) compared to marrow or peripheral blood transplants. Because antigen-presenting cells and regulatory T cells (Treg) are involved in transplant tolerance, this study was aimed at analyzing the distribution of dendritic cells (DCs) and CD14+ monocyte-specific subsets in CB and adult peripheral blood (APB) and comparing the ability of DCs from these two blood sources to induce CD4+ Treg. STUDY DESIGN AND METHODS: Myeloid DCs (mDCs), plasmacytoid DCs, the CD14+ cell subsets CD14+CD16+ and CD14+CD209+, and CD4+ T cells were analyzed by fluorescence-activated cell sorting (FACS) in whole blood. To evaluate the functionality of DCs, isolated CD3+ T cells from an adult donor were cultured with allogenic DC-enriched fraction from CB or APB, and CD4+ Treg generation was determined by FACS. Additionally, tumor necrosis factor (TNF)-alpha and interferon (IFN)-alpha release by DCs was measured. RESULTS: CB had a lesser frequency of DCs and specific CD14+ monocyte subsets than APB. After stimulation, monocytes from CB secreted less TNF-alpha than those from APB. Moreover, DCs from CB exhibited a more immature phenotype and had a decreased capacity to release TNF-alpha and IFN-alpha than those derived from APB, but on the contrary, they were efficient inducers of CD4+ T cells with a phenotype of Treg. CONCLUSION: The tolerogenic immunophenotype and diminished functionality of CB DCs can be important to create a microenvironment where Treg develop, that in turn may be relevant to observed lower incidence of chronic GVHD after CB transplantation.
Authors: Jeong-Ki Kim; Ghazi Kayali; David Walker; Heather L Forrest; Ali H Ellebedy; Yolanda S Griffin; Adam Rubrum; Mahmoud M Bahgat; M A Kutkat; M A A Ali; Jerry R Aldridge; Nicholas J Negovetich; Scott Krauss; Richard J Webby; Robert G Webster Journal: Proc Natl Acad Sci U S A Date: 2010-06-01 Impact factor: 11.205
Authors: Nadereh Naderi; Ali Akbar Pourfathollah; Kamran Alimoghaddam; Seyed Mohammad Moazzeni Journal: Clin Exp Med Date: 2008-11-01 Impact factor: 3.984
Authors: Jessica G Lee; Kathleen E Jaeger; Yoichi Seki; Yi Wei Lim; Christina Cunha; Aleksandra Vuchkovska; Alexander J Nelson; Anya Nikolai; Dan Kim; Michael Nishimura; Katherine L Knight; Paula White; Makio Iwashima Journal: Immunology Date: 2021-03-07 Impact factor: 7.215