title: Immune reconstitution after autologous hematopoietic transplantation with Lin-, CD34+, Thy-1lo selected or intact stem cell products.
abstract: In sequential studies, we compared immune reconstitution following high-dose chemotherapy (HDT) and stem cell transplantation (SCT) using intact mobilized peripheral blood stem cell (PSC) in intermediate grade non-Hodgkin's lymphoma (NHL) patients and CD34(+), lineage-negative (Lin(-)), Thy-1(lo) (CD34(+)Lin(-)Thy-1(lo)) stem cells in low-grade NHL patients. Cytokine expression and cellular phenotype and function were used as the basis of comparison. Despite differences in cellular composition of the stem cell grafts, immune reconstitution in both groups was similar. Significantly higher levels of type 1- and 2-associated cytokine messenger ribonucleic acid (mRNA) were observed both prior to and following transplant in the peripheral blood (PB) of both cohorts as compared to normal individuals. Similar levels of interleukin (IL)-4, IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) messenger ribonucleic acid (mRNA) were seen in PB mononuclear cells following transplant with either product. In contrast, patients receiving isolated CD34(+)Lin(-)Thy-1(lo) cells expressed significantly higher IL-2 levels at all times examined post-transplant. Despite the high levels of cytokine gene expression and rapid restoration to pretransplant levels of CD3 cell number by day 30, T cell function and CD4:CD8 and CD4(+)CD45RA:CD4(+)CD45RO(+) ratios were significantly depressed in both cohorts compared to normal donors, and significantly lower in patients transplanted with CD34(+)Lin(-)Thy-1(lo) compared to patients receiving an intact PSC product. These data suggest that the peripheral tolerance in patients receiving HDT and an autologous SCT occurs independent of graft composition, although immune function and CD4 recovery are better facilitated by transplantation of an intact product.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center 987660, Omaha, NE 68198-7660, USA. rsingh@unmc.edu
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Varney
authors.forename: Cheryl
authors.initials: C
authors.lastname: Leutzinger
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bierman
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ino
authors.forename: Kevin
authors.initials: K
authors.lastname: Loh
authors.forename: Craig
authors.initials: C
authors.lastname: Nichols
authors.forename: David
authors.initials: D
authors.lastname: Inwards
authors.forename: Robert
authors.initials: R
authors.lastname: Rifkin
authors.forename: James E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D003131:Combined Modality Therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000032:analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D016898:Interferon-alpha; D007378:Interleukins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma