Test ID: CD4RT
CD4 T-Cell Recent Thymic Emigrants (RTE)
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 (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 postthymectomy for malignant thymoma or as an indicator of relapse of disease (malignant thymoma) or other contexts of thymectomy
Method Name A short description of the method used to perform the test
Flow Cytometry
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Immune Competence
Immune Status, Flow Cytometry
Immunodeficiency Panel, Flow Cytometry
Recent Thymic Emigrants (RTE)
RTE (Recent Thymic Emigrants)
T-Cell
CD4 T cell Count, Flow Cytometry
Quantitative CD4 T cells
Severe Combined Immunodeficiency
Cellular Immunodeficiencies
DiGeorge syndrome
Combined immunodeficiencies
Neonatal thymic function
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 48 hours of draw. Send specimen Sunday through Thursday only. Draw and package specimen as close to shipping time as possible.
Container/Tube: Lavender top (EDTA)
Specimen Volume 3 mL
Collection Instructions:
1. Send specimen in original tube. Do not aliquot.
2. Ship specimen overnight in an Ambient Mailer-Critical Specimens Only (Supply T668).
Additional Information: Ordering physician name and phone number are required.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood EDTA | Ambient | 48 hours |
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+ naïve 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 (HCT).(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 (RRMS).(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 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/87959 T-Cell Receptor Excision Circles (TREC) Analysis for Immune Reconstitution) 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 HCT, 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 TRECs (TREC/87959 T-Cell Receptor Excision Circles (TREC) Analysis for Immune Reconstitution) for appropriate correlation of thymic output, especially in context of T cell lymphopenia, post-HCT and other cellular or combined immunodeficiencies.
Supportive Data
CD4 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
Method Description Describes how the test is performed and provides a method-specific reference
CD4 RTEs are assessed in peripheral blood drawn in EDTA tubes and the test is performed as a single-tube assay. A panel of antibodies is used for the assay: CD3, CD4, CD31, CD45RA, and CD45RO, conjugated to various fluorochromes. The blood is incubated with the antibodies in the dark, followed by RBC lysis. Absolute counts are obtained using BD TruCount tubes. The sample is then centrifuged and resuspended in a paraformaldehyde solution for analysis on a BD FACS Canto A or Canto II flow cytometer. The data analysis is performed using BD FACS Diva software. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Do not send specimen after Thursday. Specimen must be received by 10 a.m. on Friday.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
86356
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 89504 | CD4 Absolute (cells/uL) | 8127-3 |
| 29536 | CD4 RTE % | In Process |
| 29535 | CD4 RTE Absolute | In Process |
| 29178 | Interpretation | 69052-9 |
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