title: Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases).
abstract: To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA 98109-1024, USA. jstorek@fhcrc.org
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: Monja D
authors.initials: MD
authors.lastname: Metcalf
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalina
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: George H
authors.initials: GH
authors.lastname: Kraft
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology; D017690:Cell Transplantation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008231:Lymphopenia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014777:Virus Diseases / Q000150:complications / Q000276:immunology
chemical_list: D000906:Antibodies; D018952:Antigens, CD34