Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy - PubMed (original) (raw)
Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy
C L Mackall et al. N Engl J Med. 1995.
Free article
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.
Comment in
- Regeneration of T cells after chemotherapy.
Michie CA, McLean AR. Michie CA, et al. N Engl J Med. 1995 Jun 15;332(24):1651; author reply 1652. N Engl J Med. 1995. PMID: 7646663 No abstract available. - Regeneration of T cells after chemotherapy.
Cunnane G, O'Farrelly C. Cunnane G, et al. N Engl J Med. 1995 Jun 15;332(24):1650-1; author reply 1652. doi: 10.1056/NEJM199506153322414. N Engl J Med. 1995. PMID: 7753154 No abstract available. - Regeneration of T cells after chemotherapy.
Moreland LW, Bucy RP, Koopman WJ. Moreland LW, et al. N Engl J Med. 1995 Jun 15;332(24):1651-2. N Engl J Med. 1995. PMID: 7753155 No abstract available. - Age, the thymus, and T lymphocytes.
Weinberg K, Parkman R. Weinberg K, et al. N Engl J Med. 1995 Jan 19;332(3):182-3. doi: 10.1056/NEJM199501193320310. N Engl J Med. 1995. PMID: 7800012 No abstract available.
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