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Previous Volume 332:143-149 January 19, 1995 Number 3 Next

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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.

Source Information

From the Experimental Immunology Branch, Division of Cancer Biology, Diagnosis, and Centers (C.L.M., R.E.G.), the Medicine (R.E.G.) and Pediatric (M.E.H., I.T.M., A.T.S., L.H.W.) Branches, Division of Cancer Treatment, and the Biostatistics and Data Management Section (S.M.S.), National Cancer Institute; the Departments of Nuclear Medicine (M.P.A., C.C.C.), Clinical Pathology (T.A.F., M.R.B.), and Radiology (I.M.F.), Clinical Center, National Institutes of Health; and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Uniformed Services University for the Health Sciences (I.M.F.) — all in Bethesda, Md.

Address reprint requests to Dr. Mackall at Bldg. 10, Rm. 4B14, National Institutes of Health, Bethesda, MD 20892.

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Extract | Full Text  
N Engl J Med 1995; 332:1650-1652, Jun 15, 1995. Correspondence

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