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Blood, 15 February 2001, Vol. 97, No. 4, pp. 880-885
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Human equivalent of the mouse Nude/SCID phenotype: long-term
evaluation of immunologic reconstitution after bone marrow
transplantation
Claudio Pignata,
Lucia Gaetaniello,
Anna Maria Masci,
Jorge Frank,
Angela Christiano,
Eliana Matrecano, and
Luigi Racioppi
From the Departments of Pediatrics and Cellular
and Molecular Biology and Pathology, "Federico II" University,
Naples, Italy; and the Department of Dermatology and Genetics and
Development, Columbia University, New York, NY.
Human Nude/SCID (severe combined immunodeficiency) is the
first severe combined immunodeficiency caused by mutation of the winged-helix-nude (WHN) gene, which is expressed
in the thymus but not in the hematopoietic lineage. The disease is
characterized by a T-cell defect, congenital alopecia, and nail
dystrophy. A Nude/SCID patient who underwent bone marrow
transplantation from the human leukocyte antigen-identical
heterozygote brother was studied to investigate, in this unique model,
the role of the thymus in immunologic reconstitution. Despite an
increase in CD3+, CD4+, and CD8+
cells, CD4+ CD45 RA naive lymphocytes were not
regenerated. Conversely, naive CD8+ cells were normal.
After an initial recovery, lymphocyte proliferation to mitogens
progressively declined compared with controls and genotypically
identical donor cells grown in the WHN+/
environment. Analysis of the T-cell receptor (TCR) repertoire of
CD4+ cells revealed that only 3 of 18 V families had an
altered CDR3 heterogeneity length profile. Conversely, CD8+
lymphocytes showed an abnormal distribution in most V families. These data indicate that the thymus is differentially required in the
reconstitution of CD4+ and CD8+ naive subsets
and in the maintenance of their TCR repertoire complexity. Taken
together, these findings suggest that bone marrow transplantation is
ineffective in the long-term cure of this form of SCID.
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