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CD4+ CD25+ lymphocyte and dendritic cell mobilization with intermediate doses of recombinant human granulocyte
J Vela-Ojeda1, M A García-Ruiz Esparza, E Reyes-Maldonado
1Hematology Department, Stem Cell Transplant Program, Unidad Médica de Alta Especialiad Antonio Fraga Mouret Centro Médico La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico. velaj12x@prodigy.net.mx
Insights
Granulocyte colony-stimulating factor (G-CSF) effectively mobilizes key immune cells, including regulatory T cells and dendritic cells (DC), for potential therapeutic applications in cancer and autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Allogeneic hematopoietic stem cell transplantation requires effective immune cell mobilization.
- Granulocyte colony-stimulating factor (G-CSF) is used for stem cell mobilization, but its effect on specific lymphocyte subsets requires further investigation.
Purpose of the Study:
- To quantitatively and phenotypically analyze T, B, NK, NKT, DC (type 1 and 2), and regulatory T cells before and after G-CSF mobilization.
- To assess the potential of G-CSF to mobilize specific immune cell populations for therapeutic expansion.
Main Methods:
- Prospective quantitative and phenotypic analysis of lymphocyte subsets.
- Collection of stem cells from 25 HLA identical sibling donors.
- Blood sampling and flow cytometry before and after G-CSF administration (16 microg/kg/day).
Main Results:
- G-CSF significantly increased regulatory T cells (median 69 vs 161 x 10^6/L, p < 0.01).
- Observed significant increases in NK (1.7-fold, p < 0.009), NKT (1.7-fold, p < 0.02), type 1 DC (8.5-fold, p < 0.003), and type 2 DC (11.5-fold, p < 0.004).
- Successful mobilization and collection of NK, NKT, DC, and regulatory T cells for potential therapeutic use.
Conclusions:
- Intermediate doses of G-CSF effectively mobilize diverse lymphocyte subsets, notably regulatory T cells and dendritic cells.
- Mobilized cells, particularly regulatory T cells and DC, can be expanded for future use in treating cancer and autoimmune diseases.
Abstract:
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
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