Effects of granulocyte-colony-stimulating factor and granulocyte/macrophage-colony-stimulating factor administration on T cell proliferation and phagocyte cell-surface molecules during hematopoietic reconstitution after autologous peripheral blood progenitor cell transplantation.
Thirty-four ovarian and breast cancer patients received autologous peripheral blood progenitor cell transplantation after high-dose myeloablative chemotherapy and either granulocyte-colony-stimulating factor (G-CSF) or granulocyte/macrophage-colony-stimulating fictor (GM-CSF) in the immediate post-transplant period. The recovery of T cell functionality was monitored by a three-color flow-cytometric approach using carboxyfluorescein diacetate succinimidyl ester, a probe the fluorescence intensity of which halves at each round of cell replication, in conjunction with CD3 and CD25 monoclonal antibodies. There was no significant difference between the two treatments on days 12, 20, and 40, T cell proliferation always being considerably lower than that of control cultures from healthy donors. At day 80, a significantly higher proportion of mitogen-stimulated T cells from GM-CSF-treated patients expressed interleukin-2 receptor, and a higher proportion of these T cells were actively proliferating. This phenomenon did not reflect any difference in the relative proportion of various lymphocyte subsets (T cells, CD4 and CD8+ T cells, CD45RA+ and CD45RO- T cells, and natural killer cells). At the end of follow-up (1-1.5 years) T cell proliferation had returned to values typically observed in healthy individuals in both groups of patients. Soon after transplantation (day 12), neutrophils from G-CSF-treated patients had a more elevated Fcgamma receptor I density and monocytes from GM-CSF-treated patients had a more elevated Fcgamma receptor II and MHC class II molecules density. The up-modulation of Fcgamma receptor II was maintained until day 40. Thus, administering G-CSF and GM-CSF in the post-transplant period affects T lymphocyte proliferation and phagocyte membrane molecules differently.
Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy. cytogyn@rm.unicatt.it
A
A
Fattorossi
A
A
Battaglia
L
L
Pierelli
P
P
Malinconico
L
L
Andreocci
A
A
Perillo
G
G
Ferrandina
O
O
Martelli
A
A
Rughetti
M
M
Nuti
E
E
Cortesi
G
G
Scambia
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy; D010586:Phagocytes / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous
D000954:Antigens, Surface; D015704:CD4 Antigens; D010835:Phytohemagglutinins; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor