title: The effect of thymic function on immunocompetence following bone marrow transplantation.
abstract: We investigated the role of thymic function in the immunodeficiency that characterizes bone marrow transplantation (BMT) recipients. The capacity of histocompatible BMT recipients to generate new CD4+ T lymphocytes was determined by FACS analysis with antibodies to the two isoforms of CD45: CD45RA, which is expressed on newly generated CD4 T lymphocytes, and CD45RO, which is expressed on antigen-specific memory CD4 T lymphocytes. Immediately following BMT, all patients had low levels of CD45RA-expressing CD4 T lymphocytes, which increased during the first year and then stabilized. Since thymic function decreases with age in normal individuals, the impact of recipient age on the generation of new CD45RA,CD4 T lymphocytes was determined in BMT recipients with and without chronic graft-vs.-host disease (GVHD). In addition, antigen-specific immune function was determined by assessing in vitro blastogenic response to tetanus toxoid (TT). More than 1 year after transplantation, the results from BMT recipients without chronic GVHD were similar to those of normal individuals; there was an age-dependent decline in the number of CD45RA,CD4 T lymphocytes, and antigen-specific immune function was age-independent. On the other hand, recipients with chronic GVHD had an age-dependent decline in their immune function (r = 0.45 and p = 0.02) that correlated with the number of new CD45RA,CD4 T lymphocytes (p = 0.027) but not the number of memory CD45RO,CD4 T lymphocytes (p = 0.11). Thus recipients with chronic GVHD have decreased antigen-specific immune function that may be due to an acceleration of the normal thymic aging process induced by GVHD and its therapy.
authors.affiliation: Division of Research Immunology/Bone Marrow Transplantation, Children's Hospital Los Angeles, CA 90027, USA.
authors.forename: K
authors.initials: K
authors.lastname: Weinberg
authors.forename: G
authors.initials: G
authors.lastname: Annett
authors.forename: A
authors.initials: A
authors.lastname: Kashyap
authors.forename: C
authors.initials: C
authors.lastname: Lenarsky
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
authors.forename: R
authors.initials: R
authors.lastname: Parkman
mesh_terms: D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D013950:Thymus Gland / Q000276:immunology*