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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 (TBM) were less likely to express anti-CMV surface Ig than those cultured with DSPC (TSP). The flow cytometry analysis revealed an increase in the number of T4 suppressor cells (CD3+, CD4+, CD62L+) in the TBM group, whereas the T4 helper phenotype (CD3+, CD4+, CD62L-) predominated in the TSP 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.

Original languageEnglish
Pages (from-to)21-30
Number of pages10
JournalHuman Immunology
Volume64
Issue number1
DOIs
StatePublished - Jan 1 2003

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Bone Marrow Cells
B-Lymphocytes
Tissue Donors
T-Lymphocytes
CD4-Positive T-Lymphocytes
Immunoglobulins
Cadaver
Volunteers
Flow Cytometry
Spleen
In Vitro Techniques
Phenotype
B-Cell Antigen Receptors
Antibodies
Fluorescein-5-isothiocyanate
Antigen-Presenting Cells
HLA Antigens
Allografts
Cultured Cells
Cell Culture Techniques

Keywords

  • Bone marrow cells
  • PRA
  • T suppressor cells
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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.

In: Human Immunology, Vol. 64, No. 1, 01.01.2003, p. 21-30.

Research output: Contribution to journalArticle

Carreno, Manuel R. ; Fuller, Laphalle ; Mathew, James M. ; Ciancio, Gaetano ; Burke, George W ; Esquenazi, Violet ; Ricordi, Camillo ; Tzakis, Andreas G. ; Miller, Joshua. / Human donor bone marrow cells induce in vitro "suppressor T cells" that functionally suppress autologous B cells. In: Human Immunology. 2003 ; Vol. 64, No. 1. pp. 21-30.
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AU - Burke, George W

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