Restoration of T and NK cell function in GM-CSF mobilized stem cell products from breast cancer patients by monocyte depletion.
Rapid immune reconstitution is observed following autologous peripheral blood stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT), although it is depressed compared to that observed in normal individuals. The immune dysfunction occurs despite the restoration of normal lymphoid cell numbers and may be associated with the immunologic characteristics of the infused peripheral blood stem cell (PSC) product. We report herein that the in vitro T cell proliferation and NK activity in PSC products of breast cancer patients are significantly increased following the removal of CD14+ monocytes (33 +/- 2% of the PSC product) by carbonyl iron magnetic cell isolation (CI). In vitro expansion of PSC cells cultured for 7-21 days in the presence of interleukin-2 (IL-2) is also significantly increased by depletion of the phagocytic cells. The PHA and IL-2 mitogenic responses, as well as NK activity of the expanded cells, was also significantly increased by the depletion of the phagocytes. In summary, the depletion of phagocytic monocytes from PSC products restores the proliferative and functional properties of T and NK lymphocytes and may facilitate adoptive cellular therapy, as well as rapid immunologic reconstitution post-PSCT.
Ageitos
A G
AG
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Ino
K
K
Ozerol
I
I
Tarantolo
S
S
Heimann
D G
DG
Talmadge
J E
JE
D001943:Breast Neoplasms / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D009000:Monocytes; D010586:Phagocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor