T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells

D. Rondelli, C. Anasetti, A. Fortuna, M. Ratta, M. Arpinati, G. Bandini, R. M. Lemoli, S. Tura

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In this study, the hypothesis that a subset of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ blood cells may actively induce an allogeneic T cell response in vitro was tested. Circulating CD34+ cells were purified to ≤ 98% by high gradient magnetic separation and then analyzed for the coexpression of HLA-DR, the common P-chain of the leukointegrin family CD18 and costimulatory molecules CD80 (B7-1) and CD86 (B7-2). These antigens were expressed on average on: 94.9 ± 2.5%, 64.4 ± 15.4%, 0% and 1.9 ± 1.2% CD34+ blood cells, respectively. Irradiated CD34+ cells induced a high proliferative response of allogeneic, but not autologous, purified CD4+ and CD8+ T cells in primary mixed leukocyte culture (MLC). An average three-fold lower CD4+ and CD8+ T cell response was induced by mononuclear cells from G-CSF-treated donors. A lower frequency of allostimulating cells among mononuclear cells rather than among CD34+ cells in the apheresis was documented by limiting dilution assay (LDA). As previously observed with marrow, sorted CD34+/CD18+ cells induced the proliferation of allogeneic T cells in MLC, while CD34+/CD18- cells, which were > 94% HLA-DR+ and contained both committed (CFU-C) and early (LTC-IC) hematopoietic progenitors, stimulated allogeneic T cells poorly. Three-color staining cytofluorimetry indicated that expression of CD80 and CD86 were upregulated in 6.9 ± 4.9 and 10.7 ± 2.6% CD34+ blood cells respectively, after 24-30 h of culture with autologous or allogeneic mononuclear cells, or with CD4+, or CD8+ T cells, but not with medium alone. Moreover, the upregulation of CD86 was observed on CD34+/CD18+ rather than on CD34+/CD18- cells after 30 h in MLC. Blocking experiments demonstrated that preincubation of stimulator and responder cells with anti-CD80 plus anti-CD86 monoclonal antibodies induced a 84 ± 8% inhibition of CD34+ cell allostimulating activity after 6 days in primary MLC. These results suggest that G-CSF-mobilized CD34+ hematopoietic progenitors with alloantigen presenting function express CD18 and may upregulate CD80 and CD86 upon interaction with T cells. Since activation of B7 costimulatory molecules represents an active costimulatory pathway on G-CSF-mobilized CD34+ cells, the blockade of these molecules or, alternatively, the use of selected non-immunogenic CD34+/CD18- blood stem cells may represent a new strategy for reducing graft rejection and overcoming HLA barriers in allogeneic stem cell transplantation.

Original languageEnglish
Pages (from-to)1183-1191
Number of pages9
JournalBone Marrow Transplantation
Volume21
Issue number12
Publication statusPublished - 1998

Fingerprint

Granulocyte Colony-Stimulating Factor
Blood Cells
T-Lymphocytes
Leukocytes
HLA-DR Antigens
Up-Regulation
CD80 Antigens
B7 Antigens
Blood Component Removal
Isoantigens
Graft Rejection
Stem Cell Transplantation
Stem Cells
Color
Bone Marrow
Monoclonal Antibodies
Cell Proliferation
Staining and Labeling
Antigens

Keywords

  • Alloreactivity
  • B7-1
  • B7-2
  • CD18
  • G-CSF
  • Hematopoietic progenitors

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Rondelli, D., Anasetti, C., Fortuna, A., Ratta, M., Arpinati, M., Bandini, G., ... Tura, S. (1998). T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells. Bone Marrow Transplantation, 21(12), 1183-1191.

T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells. / Rondelli, D.; Anasetti, C.; Fortuna, A.; Ratta, M.; Arpinati, M.; Bandini, G.; Lemoli, R. M.; Tura, S.

In: Bone Marrow Transplantation, Vol. 21, No. 12, 1998, p. 1183-1191.

Research output: Contribution to journalArticle

Rondelli, D, Anasetti, C, Fortuna, A, Ratta, M, Arpinati, M, Bandini, G, Lemoli, RM & Tura, S 1998, 'T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells', Bone Marrow Transplantation, vol. 21, no. 12, pp. 1183-1191.
Rondelli D, Anasetti C, Fortuna A, Ratta M, Arpinati M, Bandini G et al. T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells. Bone Marrow Transplantation. 1998;21(12):1183-1191.
Rondelli, D. ; Anasetti, C. ; Fortuna, A. ; Ratta, M. ; Arpinati, M. ; Bandini, G. ; Lemoli, R. M. ; Tura, S. / T cell alloreactivity induced by normal G-CSF-mobilized CD34+ blood cells. In: Bone Marrow Transplantation. 1998 ; Vol. 21, No. 12. pp. 1183-1191.
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