title: Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy.
abstract: BACKGROUND
  Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway.
  
  
  METHODS
  We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly.
  
  
  RESULTS
  There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r = -0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r = 0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P = 0.015).
  
  
  CONCLUSIONS
  Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: C L
authors.initials: CL
authors.lastname: Mackall
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: M P
authors.initials: MP
authors.lastname: Andrich
authors.forename: C C
authors.initials: CC
authors.lastname: Chen
authors.forename: I M
authors.initials: IM
authors.lastname: Feuerstein
authors.forename: M E
authors.initials: ME
authors.lastname: Horowitz
authors.forename: I T
authors.initials: IT
authors.lastname: Magrath
authors.forename: A T
authors.initials: AT
authors.lastname: Shad
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000096:biosynthesis; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D012509:Sarcoma / Q000188:drug therapy; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens