CD8 T-Cell Immune Competence, Global, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Determining overimmunosuppression within the CD8 T-cell compartment, when used on transplant recipients and patients with autoimmune disorders receiving therapy with immunosuppressant agents
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
CD8 Immune Competence, B
Global Immune Competence
Specimen Type Describes the specimen type needed for testing
WB Sodium Heparin
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.
It is recommended that specimens arrive within 24 hours of draw. Specimens are required to be received in the laboratory on weekdays and by 4 p.m. on Friday. No weekend processing. Draw and package specimen as close to shipping time as possible.
Container/Tube: Green top (sodium heparin)
Specimen Volume: 15 mL
Collection Instructions: Ship specimen overnight in an Ambient Mailer-Critical Specimens Only (Supply T668).
1. Ordering physician's name and phone number are required.
2. For serial monitoring, we recommend that specimen draws be performed at the same time of day.
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.
Mild OK; Gross reject
Mild OK; Gross reject
Green-top (lithium heparin) tube
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|WB Sodium Heparin||Ambient||48 hours|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
CD8 T cells play an important role in the immune response to viral or intracellular infectious agents, as well as antitumor immunity and immune surveillance.
Upon activation, CD8 T cells mediate a variety of effector functions, including cytokine secretion and cytotoxicity. Interferon-gamma (IFN-gamma) is 1 of the early cytokines produced by CD8 T cells; it is released within a few hours of activation.(1) The cytotoxic function is mediated by the contents of the cytolytic granules.(1) Cell-surface mobilization of the cytolytic granule components, CD107a and CD107b, also known as lysosome-associated membrane proteins LAMP-1 and LAMP-2, occurs when CD8 T cells mediate their cytolytic function and degranulate.(2)
CD8 T-cell activation occurs either through the T-cell receptor (TCR)-peptide-major histocompatibility complex (MHC) or by use of a mitogen (eg, phorbol myristate acetate and the calcium ionophore ionomycin). Mitogen-mediated activation is antigen nonspecific.
Impairment of global CD8 T-cell activation (due to inherent cellular immunodeficiency or as a consequence of over-immunosuppression by therapeutic agents) results in reduced production of IFN-gamma and other cytokines, reduced cytotoxic function, and increased risk for developing infectious complications. Agents associated with over-immunosuppression include the calcineurin inhibitors (eg, cyclosporine A, FK506 [Prograf/tacrolimus], and rapamycin [sirolimus]), antimetabolites (eg, mycophenolate mofetil), and Thymoglobulin.
Immunosuppression is most commonly used for allograft maintenance in solid organ transplant recipients, to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplant patients and to treat patients with autoimmune diseases. In these settings, reducing the risk for developing infectious complications as a result of over-immunosuppression is a clinical challenge.
Therapeutic drug monitoring (TDM) is routinely used in the transplant practice to avoid overtreatment and to determine patient compliance. But, the levels of drugs measured in blood do not directly correlate with the administered dose due to individual pharmacokinetic differences.(3) Furthermore, drug levels may not necessarily correlate with biological activity of the drug. Consequently, it may be beneficial to consider modification of the immunosuppression regimen based on the patient's level of functional immune competence.
This assay provides a means to evaluate over-immunosuppression within the CD8 T-cell compartment (global CD8 T-cell function). Intracellular IFN-gamma expression is a marker for CD8 T-cell activation. Surface CD107a and CD107b are markers for cytotoxic function. This test may be most useful when ordered at the end of induction immunosuppression and 2 to 3 months after maintenance immunosuppression to ensure that global CD8 T-cell function is not compromised. The test may also provide value when immunosuppression is increased to halt or prevent graft rejection, to provide information on a balance between over-immunosuppression with subsequent infectious comorbidities and under-immunosuppression with resultant graft rejection.
The absolute counts of lymphocyte subsets are known to be influenced by a variety of biological factors, including hormones, the environment, and temperature. The studies on diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase in CD4 T cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8:30 a.m. and noon with no change between noon and afternoon. Natural Killer (NK) cell counts, on the other hand, are constant throughout the day.(4) Circadian variations in circulating T-cell counts have been shown to be negatively correlated with plasma cortisol concentration.(5,6,7) In fact, cortisol and catecholamine concentrations control distribution and therefore, numbers of naive versus effector CD4 and CD8 T cells.(5) It is generally accepted that lower CD4 T cell counts are seen in the morning compared to the evening(8) and during summer compared to winter.(9) These data therefore indicate that timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets.
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.
Interferon-gamma (IFN-gamma) expression (as % CD8 T cells): 10.3-56.0%
CD107a/b expression (as % CD8 T cells): 8.5-49.1%
Reference values have not been established for patients who are <18 years of age.
Interferon-gamma (IFN-gamma) and CD107a and CD107b expression below the defined reference range are consistent with a global impairment in CD8 T-cell function, most likely due to overimmunosuppression.
IFN-gamma and CD107a and CD107b levels greater than the defined reference range are unlikely to have any clinical significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay is specific only for CD8 T cells; it does not provide information for overall T-cell competence.
Further studies are needed to determine if, within the reference range, certain levels of Interferon-gamma and CD107a and b expression confer greater or lesser degrees of risk for infectious disease.
Timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets. See data under Clinical Information.
The 95% confidence interval reference values were determined from 102 healthy adult donors.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Betts MR, Casaza JP, Patterson BA, et al: Putative immunodominant human immunodeficiency virus-specific CD8 T-cell responses cannot be predicted by MHC class I haplotype. J Virol. 2000 Oct;74(19):9144-9151
2. Peters PJ, Borst J, Oorschot V, et al: Cytotoxic T-lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med. 1991 May 1;173(5):1099-1109
3. Venkataramanan R, Shaw LM, Sarkozi L, et al: Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 2001 May;41(5):542-551
4. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract # B11052
5. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009;113:5134-5143
6. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411
7. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Pyschosom Med 1997;59:42-50
8. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151
9. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516
Method Description Describes how the test is performed and provides a method-specific reference
Peripheral blood mononuclear cells (PBMC), which contain CD8 T cells, are stimulated with a mixture of phorbol myristate acetate (PMA) and ionomycin, and with stimulatory signals derived using antibodies against the costimulatory molecules CD28/CD49d. The cells are simultaneously treated with a mixture of brefeldin A (BFA) and monensin, which blocks extracellular secretion of interferon-gamma (IFN-gamma), enabling intracellular retention and detection of the protein. PBMCs that have not been stimulated are used as a control to determine the background levels of IFN-gamma and CD107a and CD107b. The cells are analyzed on the BD FACSCanto flow cytometer and analysis involves gating (defining) of the CD8 T cells using an antihuman CD8 antibody. Specific IFN-gamma and CD107a and CD107b signals are determined within the "gated" CD8 T-cell population. Global CD8 T-cell immune competence is measured by the amount of IFN-gamma produced (CD8 T-cell functional activity) and surface expression of CD107a and CD107b (cytotoxicity assessment) relative to the unstimulated control and is interpreted on the basis of the reference range determined from healthy adult donors.(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
Specimens are required to be received in the laboratory on weekdays and by 4 p.m. on Friday. No weekend processing
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
PBMC's are stored for 7 days at -70 degrees C.
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.
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
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 x 2
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|