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Human donor bone marrow cells induce in vitro “suppressor T cells” that functionally suppress autologous B cells

Carreno, Manuel R ; Fuller, Laphalle ; Mathew, James M ; Ciancio, Gaetano ; Burke, George W ; Esquenazi, Violet ; Ricordi, Camillo ; Tzakis, Andreas G ; Miller, Joshua

Human immunology, 2003, Vol.64 (1), p.21-30 [Peer Reviewed Journal]

United States: Elsevier Inc

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  • Title:
    Human donor bone marrow cells induce in vitro “suppressor T cells” that functionally suppress autologous B cells
  • Author: Carreno, Manuel R ; Fuller, Laphalle ; Mathew, James M ; Ciancio, Gaetano ; Burke, George W ; Esquenazi, Violet ; Ricordi, Camillo ; Tzakis, Andreas G ; Miller, Joshua
  • Subjects: Bone Marrow - immunology ; bone marrow cells ; Bone Marrow Cells - immunology ; Bone Marrow Transplantation - immunology ; Cell Culture Techniques ; Humans ; PRA ; T suppressor cells ; T-Lymphocyte Subsets - immunology ; transplantation ; Transplantation Tolerance - immunology ; Transplantation, Homologous
  • Is Part Of: Human immunology, 2003, Vol.64 (1), p.21-30
  • Notes: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
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    ObjectType-Article-1
    ObjectType-Feature-2
  • Description: We have reported a beneficial effect of donor vertebral body bone marrow cells (DBMC) infusions in cadaver renal allograft recipients in a 6-year follow-up, but with a transient increase in early (6 month) postoperative CMV infections and concomitant suppressed immunoglobulins (Ig) production. We also found that although there was no difference between the DBMC-infused and non-infused (control) groups in the development of donor-specific antibody, we now describe an additional difference seen in the percent reactive antibody (PRA) reactivity against a panel of HLA antigens that developed postoperatively. We hypothesize that (allogeneic) antigen presenting cells in the DBMC, systemically infused, caused the generation of recipient T suppressor (T4-suppressor) cells, thereby “inducing” a negative influence on B cell Ig production. We tested this notion in vitro by incubating PBL from CMV IgG positive laboratory volunteers with either (allogeneic) T-cell depleted DBMC or donor spleen cells (DSPC) from (the same) cadaver donors. After 7 days, the (responding) T cells were collected using magnetic beads and placed in culture with purified B cells freshly obtained from the same (autologous) CMV positive volunteer. To these cultures were added either media or 40 ng of CMV antigen. After 3, 5, 7, and 9 days, the expression of surface anti-CMV Ig was measured by flow cytometry using a panel of fluorescent markers double-labeled for activated B cells (CD20, CD19, and HLA DRw) and CMV-FITC. We also determined the phenotype of the cultured T cells using anti-CD3, CD4, and CD62L specific monoclonal antibodies. B cells that had been in contact with autologous T cells derived from DBMC cultures (T BM) were less likely to express anti-CMV surface Ig than those cultured with DSPC (T SP). The flow cytometry analysis revealed an increase in the number of T4 suppressor cells (CD3 +, CD4 +, CD62L +) in the T BM group, whereas the T4 helper phenotype (CD3 +, CD4 +, CD62L −) predominated in the T SP group. These in vitro findings support the notion that (allogeneic) DBMC infusions can induce a T4 suppressor (regulatory) influence and thereby indirectly affect B-cell function.
  • Publisher: United States: Elsevier Inc
  • Language: English
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