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continue to possess high levels of TREC despite an age-related tenfold reduction from neonatal to older
age.(6) CD4 RTEs (CD31+CD4+CD45RA+) have longer telomeres and higher telomerase activity,
which, along with the increased TREC levels, suggest a population of T cells with low replicative
history.(6) CD31+CD4+ T cells are an appropriate cell population to follow to evaluate thymic
reconstitution in lymphopenic children post-hematopoietic stem cell transplant (HSCT).(6) A Mayo study
showed that the CD31 marker correlates with TREC-enriched T cells across the spectrum of age and
correlates with thymic recovery in adults after autologous stem cell transplantation.(7) CD31+ CD4 RTEs
have also been used to evaluate T-cell homeostatic anomalies in patients with relapsing-remitting multiple
sclerosis (RRMS).(8) There is an age-related decline in the numbers of CD103+CD62L+CD8 RTE, which
also can be precipitated by thymectomy or loss of thymic function.(5) Additionally, these cells are quite
short-lived in the periphery.(5,7) A Mayo study showed that in adults over the age of 20 there is no linear
correlation between CD8 RTE expressing CD103 and CD62L and TREC levels, suggesting that
homeostasis in the CD8 T-cell compartment is probably maintained more by peripheral expansion than by
thymic output.(7) This concept may be corroborated by the fact that CD8 T-cell counts recover
numerically more rapidly post-HSCT than CD4 T cells, resulting in a skewed CD4:CD8 ratio for several
months to 1 year posttransplant, and that increase in CD4 T-cell counts coincides with associated thymic
recovery. Serial measurements are recommended for most clinical contexts since a single TREC
measurement may have little clinical value. For HSCT patients, thymopoiesis evaluation ideally should be
performed every 3 months in the first year and every 6 months in the second year following
transplantation. For HIV patients on highly active antiretroviral therapy (HAART), this assay every 3 to 4
months would be helpful. For patients with DiGeorge syndrome (DGS)--a cellular immunodeficiency
associated with other congenital problems including cardiac defects, facial dysmorphism,
hypoparathyroidism, and secondary hypocalcemia, and chromosome 22q11.2 deletion (in a significant
proportion of patients)--measurement of thymic function provides valuable information on the functional
phenotype, ie, complete DGS (associated with thymic aplasia) or partial DGS (generally well-preserved
thymic function). Thymus transplants have been performed in patients with complete DGS but are not
required in partial DGS.
Useful For: Evaluating thymic reconstitution in patients following hematopoietic stem cell
transplantation, chemotherapy, biological or immunomodulatory therapy, and immunosuppression
Evaluating thymic recovery in HIV-positive patients on highly active antiretroviral therapy (HAART)
Evaluating thymic output in patients with DiGeorge syndrome or other cellular immunodeficiencies
Assessing the naive T-cell compartment in a variety of immunological contexts: autoimmunity, cancer,
immunodeficiency, and transplantation Identification of thymic remnants post-thymectomy for malignant
thymoma or as an indicator of relapse of disease (malignant thymoma) The CD8 RTE test has limited
value in the clinical interpretation of recent thymic output in adults (see Cautions), and is likely to be of
more clinical relevance in pediatric individuals
Interpretation: The absence or reduction of T-cell receptor excision circle (TRECs), CD31+CD4
recent thymic emigrants (RTEs), and CD8+CD103+ RTEs correlates with loss of or reduced thymic
output and changes in the naive CD4 T-cell compartment. CD4 RTEs measured along with CD8 RTEs
and TREC provides a comprehensive assessment of thymopoiesis. Conversely, increases in CD8 RTEs
are of no clinical significance, and do not indicate a pathologic finding. Since CD8 RTEs is a rare
population, small changes in serial measurements may result in some values being above the reference
range; however, as noted, increases in CD8 RTEs do not have clinical significance. To evaluate immune
reconstitution or recovery of thymopoiesis post-T-cell depletion due to HSCT, immunotherapy, or other
clinical conditions, it is essential to serially measure CD4, CD8 RTE, and TREC levels. TRECs generally
show an inverse correlation with age, though there can be substantial variations in TREC count within a
given age group. Additionally, in most relevant clinical settings, a single measurement for thymic
function has very little value in discerning thymic reconstitution. Serial measurements are recommended
and the frequency can vary depending on the clinical context. A consultative report is provided.
Reference Values:
T-CELL RECEPTOR EXCISION CIRCLES (TREC) ANALYSIS FOR IMMUNE RECONSITUTION
T & B Absolute Counts
T Cells (CD3)
0-2 months: 2,500-5,500 cells/mcL*
3-5 months: 2,500-5,600 cells/mcL*
6-11 months: 1,900-5,900 cells/mcL*
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1739