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Effacing of the T Cell Compartment by Cardiac Transplantation in Infancy¹

Brenda M. Ogle^*,, Lori J. West^**, David J. Driscoll, Scott E. Strome, Raymund R. Razonable^,¶, Carlos V. Paya, Marilia Cascalho^*,,||,# and Jeffrey L. Platt^2,*,,||,#

^* Transplantation Biology Program and the Department of Physiology, Department of Pediatrics, Department of Infectious Diseases, ^¶ Department of Internal Medicine, ^|| Department of Immunology, and ^# Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905; ^** Department of Pediatrics, Hospital for Sick Children Research Institute and University of Toronto, Toronto, Ontario, Canada; and Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, MD 21201

For cardiac transplantation in infants, T cells are depleted and the thymus is removed. These manipulations should cause profound defects in the T cell compartment. To test this concept, 20 subjects who underwent cardiac transplantation in infancy and healthy age-matched subjects were studied. The number of T cells in the blood was nearly normal in all subjects 1–10 years after surgery. However, newly generated T cells were undetectable in 10 recipients and 10-fold less than controls in 10, suggesting absence of thymic function. TCR chain diversity, measured by a novel technique, was 100-fold lower than controls. T cell function, deduced from levels of human herpesvirus 7 and response to hepatitis B immunization, were notably impaired. Yet cardiac transplant recipients were generally free of opportunistic infections. Our findings demonstrate a novel approach to measuring lymphocyte diversity and suggest that understanding how these subjects resist infection could yield important insights into immune fitness.

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