876 Comparative Effects of Surgical Thymectomy and Perinatal HIV Infection on Parameters of Thymopoiesis in Children and Adolescents P. Krogstad*1, N. Halnon1, B. Jamieson1, M. Belzer2, J. Church2 1David Geffen Sch of Med at UCLA, Los Angeles, CA and 2Childrens Hosp, Los Angeles, CA
Background: The size and activity of the thymus is greatest in early childhood, yet retains some function well into adulthood. Although other data suggest that extrathymic sites of T-cell development also exist, perinatal HIV-infection and early thymectomy, if complete, could potentially abrogate normal T-cell development. We have investigated the effects of perinatal HIV-1 infection and surgical thymectomy on the peripheral T-cell repertoire.
Methods: Fifteen (15) children with congenital heart disease (CHD) who had undergone midline cardiac surgery more than 1 yr earlier were enrolled at the time of presentation for additional palliative or corrective cardiothoracic surgery. Subjects with DiGeorge or velocardiofacial syndromes or 22q11 deletions were excluded. At surgery, blood was collected for lymphocyte subset analysis and measurement of TCR recombination excision circles (TREC) in PBMC. At surgery, an observer blinded to the laboratory study noted the presence and estimated volume of thymic tissue present. T-lymphocyte subsets were quantified by flow cytometry, and TREC were quantified by Real Time PCR. Similarly, TREC and lymphocyte subsets were quantified in PBMC of perinatally infected adolescents (PIA) (n = 15; mean 16 yrs of age), 24 seronegative adolescents (SNA), and 10 children who were to undergo similar procedures for correction of CHD, but who had not prior surgery.
Results: Unexpectedly, children with CHD who had not had prior surgery were consistently found to have CD4+ and CD8+ lymphocyte counts near the 10th to 25th percentile for age and PBMC TREC values that were 4-fold lower than the SNA. Children with prior surgery and visible thymus at the time of the 2nd operation also had low CD4+ and CD8+ T-cell counts (mean: 370/750 cells/ml, resp), and TREC values that were 3-fold below the SNA. Children with prior surgery and no residual thymus had similarly low T-cell counts, and 5 of 6 had undetectable TREC values. In contrast, the PIA had detectable TREC values, within 2-fold of the mean for SNA.
Conclusions: Surgical ablation of the thymus in early childhood markedly diminished TREC, a parameter of thymic activity. Thus, we found no evidence of a compensatory extrathymic source of T-cell production in children who underwent thymectomy in early childhood. However, we found evidence of significant thymic activity in PIA, suggesting that HIV-induced involution of the thymus may be uncommon in adolescent survivors of perinatal infection.