Immune Reconstitution

Following UCBT, B-cell recovery is commonly regained within weeks, while T-cell competence is often not complete for 12-36 or more months. Quantitative assessment of immune reconstitution may be performed by determining lymphocyte subset counts. Qualitative determination may be undertaken by evaluation of T-cell-receptor excision circles (TRECs)—stable, nonreplicating episomal DNA byproducts of the TCR rearrangement process. TRECs provide an estimate of the thymus's ability to produce new T cells.40 Analysis of TCR Vp-chain complimentary determining region 3 (CDR3) is a measure of TCR diversity.41

Quantitative immune reconstitution in children the first 100 days post-UCBT has been evaluated.42 B-cell counts increased to normal levels 30-90 days post-transplant as did serum immunoglobulin levels. NK cell counts remained within the normal range during the first 100 days. CD4+ and CD8+ T-cell counts did not recover during this period. Additional pediatric patients were followed several months post-UCBT.43 CD4+ and CD8+ cells recovered at medians of 12 and 9 months. Multivariate analysis of factors affecting lymphocyte subsets revealed that GVHD had an adverse affect on CD4+ recovery. Recipients of unrelated-donor grafts had worse CD8+ recovery. A separate analysis in children found that naïve and memory T-cell counts reached normal levels between 6 and 12 months post-UCBT in children. In adults, CD4+ and CD8+ T cells did not reach normal levels until 2 years post-UCBT, while naïve and memory T-cell recovery were delayed until 3 years post-UCBT.44 TREC determination and Vp-chain TCR CDR3 analysis following UCBT has been assessed in both children and adults.44 45 TREC levels and Vp-chain TCR diversity were limited in both populations in the first 2-6 months post-UCBT. In children, TCR diversity broadened as early as 9 months; TREC levels were detectable 1 year post-UCBT. In adults, development of TCR diversity was delayed until nearly 3 years post-UCBT. TREC levels were first detected at 18 months. Increasing TREC levels in both children and adults coincided with the appearance of naïve CD4+ T cells. These data suggest that the antigen-driven peripheral expansion of T cells following pediatric UCBT is more short lived as a result of earlier thymic-dependent immune reconstitution. Following adult UCBT, thymic-dependent immune reconstitution is more delayed.

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