title: Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia.
abstract: Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand pre-existing memory T cells.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. nicholas_haining@dfci.harvard.edu
authors.forename: W Nicholas
authors.initials: WN
authors.lastname: Haining
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Heather L
authors.initials: HL
authors.lastname: Keczkemethy
authors.forename: John W
authors.initials: JW
authors.lastname: Evans
authors.forename: Stephen
authors.initials: S
authors.lastname: Rivoli
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Howard M
authors.initials: HM
authors.lastname: Rosenblatt
authors.forename: William T
authors.initials: WT
authors.lastname: Shearer
authors.forename: Javier
authors.initials: J
authors.lastname: Guenaga
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
authors.forename: Eva C
authors.initials: EC
authors.lastname: Guinan
authors.forename: Lee M
authors.initials: LM
authors.lastname: Nadler
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007231:Infant, Newborn; D009026:Mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis; D013946:Thymopoietins / Q000276:immunology; D013997:Time Factors
chemical_list: D013946:Thymopoietins