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Test ID: CD4RT    
CD4 T-Cell Recent Thymic Emigrants (RTE)

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Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluating thymic reconstitution in patients following hematopoietic cell transplantation, chemotherapy, immunomodulatory therapy, and immunosuppression

 

Evaluating thymic recovery in HIV-positive patients on highly active antiretroviral therapy

 

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 postthymectomy for malignant thymoma or as an indicator of relapse of disease (malignant thymoma) or other contexts of thymectomy

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Naive T-cells are generated in the thymus and exported to peripheral blood to form the peripheral T-cell repertoire. There is a decrease in naive T cells derived from the thymus with age due to age-related decline in thymic output. Recent thymic emigrants (RTEs) typically refers to those populations of naive T cells that have not diluted their TREC copies (T-cell receptor excision circles) by homeostatic or antigen-driven cell division. Naive T cells can be long-lived in the periphery and postpuberty, and in adults, peripheral T-cell homeostasis is maintained by a balance of thymic output and peripheral T-cell expansion and this proportion changes with age. In infants and prepubertal children, the T-cell repertoire is largely maintained by thymic-derived naive T cells. RTEs express TRECs indicative of naive T cells derived from the thymus.(1) In the CD4 T-cell compartment it has been shown that naive CD45RA+ T cells coexpressing CD31 had a higher frequency of TREC compared to T cells lacking CD31.(2) The higher proportion of TREC+ naive T cells indicate a more recent thymic ontogeny since TRECs can be diluted by cell division (since they are extrachromosomal).  

 

It has been shown that CD31+CD4+ T cells continue to possess a relatively higher proportion of TREC despite an age-related 10-fold reduction after the neonatal period.(3) CD4 RTEs (CD31+CD4+CD45RA+) have longer telomeres and higher telomerase activity, which, along with the increased frequency of TREC positivity suggests a population of T cells with low replicative history.(3) The same study has also shown that CD31+ CD4+ T cells are an appropriate cell population to evaluate thymic reconstitution in lymphopenic children posthematopoietic cell transplant.(3) A Mayo study (unpublished) shows that the CD31 marker correlates with TREC-enriched T cells across the spectrum of age and correlates with thymic recovery in adults after autologous hematopoietic cell transplantation.(4) CD31+ CD4 RTEs have also been used to evaluate T-cell homeostatic anomalies in patients with relapsing-remitting multiple sclerosis.(5)

 

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 in a minority of patients) or partial DGS (generally well-preserved thymic function seen the in the majority of patients). Thymus transplants have been performed in patients with complete DGS, but are typically not required in partial DGS. There can be change in peripheral T-cell counts in DGS patients with age.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

CD4 ABSOLUTE

Males

1 month-17 years: 153-1,745 cells/mcL

18-70 years: 290-1,175 cells/mcL

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

Females

1 month-17 years: 582-1,630 cells/mcL

18-70 years: 457-1,766 cells/mcL

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

 

CD4 RTE %

Males

1 month-17 years: 19.4-60.9%

18-25 years: 6.4-51.0%

26-55 years: 6.4-41.7%

> or =56 years: 6.4-27.7%

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

Females

1 month-17 years: 25.8-68.0%

18-25 years: 6.4-51.0%

26-55 years: 6.4-41.7%

> or =56 years: 6.4-27.7%

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

 

CD4 RTE ABSOLUTE

Males

1 month-17 years: 50.0-926.0 cells/mcL

18-70 years: 42.0-399.0 cells/mcL

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

Females

1 month-17 years: 170.0-1,007.0 cells/mcL

18-70 years: 42.0-832.0 cells/mcL

Reference values have not been established for patients that are <30 days of age.

Reference values have not been established for patients that are >70 years of age.

Interpretation Provides information to assist in interpretation of the test results

The absence or reduction of CD31+CD4 recent thymic emigrants (RTEs) generally correlates with loss or reduced thymic output and changes in the naive CD4 T-cell compartment, especially in infancy and prepubertal children. The CD4RTE result has to be interpreted more cautiously in adults due to age-related decline in thymic function and correlated with total CD4 T cell count and other relevant immunological data. CD4 RTEs measured along with TREC (TREC / T-Cell Receptor Excision Circles (TREC) Analysis, Blood) provides a comprehensive assessment of thymopoiesis, but should not be used in adults over the sixth decade of life as clinically meaningful information on thymic function is limited in the older population due to a physiological decline in thymic activity.

 

To evaluate immune reconstitution or recovery of thymopoiesis post-T-cell depletion due to posthematopoietic cell transplant, immunotherapy, or other clinical conditions, it is helpful to systematically (serially) measure CD4RTE, and TREC copies in the appropriate age groups.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The CD4 recent thymic emigrants (RTE) assay is likely to be most helpful when used along with measurement of T-cell receptor excision circles (TREC / T-Cell Receptor Excision Circles (TREC) Analysis, Blood) for appropriate correlation of thymic output, especially in context of T cell lymphopenia, post-posthematopoietic cell transplant and other cellular or combined immunodeficiencies.

Supportive Data

CD4 recent thymic emigrant (RTE) pediatric reference values (95% confidence intervals) were obtained by evaluating 90 healthy individuals, ages 1 month to 17 years. There was no significant age relationship for CD4 RTE. Gender relationships for CD4 RTE were significant at the 50th percentile (p< or =0.0001). Adult reference values (95% confidence intervals) were obtained by evaluating 168 healthy adults, ages 18 to 70 years. There were significant age relationships for CD4 RTE as % CD4 T-cells.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Hassan J, Reen DJ: Human recent thymic emigrants-identification, expansion, and survival characteristics. J Immunol 2001;167:1970-1976

2. Kimmig S, Przybylski GK, Schmidt CA, et al: Two subsets of naive T-helper cells with distinct T-cell receptor excision circle content in human adult peripheral blood. J Exp Med 2002;195(6):789-794

3. Junge S, Kloeckener-Gruissem B, Zufferey R, et al: Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4 T-cells in normal individuals during aging and in lymphopenic children. Eur J Immunol 2007;37:3270-3280

4. Dong X, Hoeltzle MV, Abraham RS: Evaluation of CD4 and CD8 recent thymic emigrants in healthy adults and children. Unpublished data 2008

5. Duszczyszyn DA, Beck JD, Antel J, et al: Altered naiveCD4 and CD8 T-cell homeostasis in patients with relapsing-remitting multiple sclerosis: thymic versus peripheral (non-thymic) mechanisms. Clin Exp Immunol 2005;143:305-313