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Lymphocytes in peripheral blood (circulation) are heterogeneous and can be broadly classified into T cells, B cells, and natural killer (NK) cells. There are various subsets of each of these individual populations with specific cell-surface markers and function. This assay provides absolute (cells/mcL) and relative (%) quantitation for total T cells and CD4+ and CD8+ T-cell subsets, in addition to a total lymphocyte count (CD45+).
Each of these lymphocyte subpopulations have distinct effector and regulatory functions and are maintained in homeostasis under normal physiological conditions. Each of these lymphocyte subsets can be identified by a combination of 1 or more cell surface markers. The CD3 antigen is a pan T-cell marker, and T cells can be further divided into 2 broad categories, based on the expression of CD4 or CD8 coreceptors.
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 increase between 8:30 a.m. and noon with no change between noon and afternoon.(1) Circadian variations in circulating T-cell counts have been shown to be negatively correlated with plasma cortisol concentration.(2-4) In fact, cortisol and catecholamine concentrations control distribution and, therefore, numbers of naive versus effector CD4 and CD8 T cells.(2) It is generally accepted that lower CD4 T-cell counts are seen in the morning compared to the evening(5) and during summer compared to winter.(6)
These data therefore indicate that timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets.
Abnormalities in the number and percent of CD3, CD4, and CD8 T cells have been described in a number of different disease conditions. In patients who are infected with HIV, the CD4 count is measured for AIDS diagnosis and for initiation of antiviral therapy. The progressive loss of CD4 T lymphocytes in patients infected with HIV is associated with increased infections and complications. The Public Health Service has recommended that all HIV-positive patients be tested every 3 to 6 months for the level of CD4 T lymphocytes.
Basic T-cell subset quantitation is also very useful in the evaluation of patients with primary cellular immunodeficiencies of all ages, including follow-up for newborn screening for severe combined immunodeficiency and immune monitoring following immunosuppressive therapy for transplantation, autoimmunity, or any other relevant clinical condition where immunomodulatory treatment is used, and the T-cell compartment is specifically affected.
It is also helpful as a preliminary screening assay for gross quantitative anomalies in T cells, whether related to malignancies or infection.
Serial monitoring of CD4 T-cell count in HIV-positive patients
Follow-up and diagnostic evaluation of primary cellular immunodeficiencies, including severe combined immunodeficiency
T-cell immune monitoring following immunosuppressive therapy for transplantation, autoimmunity, and other immunological conditions where such treatment is utilized
Assessment of T-cell immune reconstitution post hematopoietic cell transplantation
Early screening of gross quantitative anomalies in T cells in infection or malignancies
HIV treatment guidelines from the US Department of Health and Human Services and the International Antiviral Society-USA Panel recommend antiviral treatment in all patients with HIV infection, regardless of CD4 T-cell count.(7,8) Additionally, antibiotic prophylaxis for Pneumocystis jiroveci infection and other opportunistic infections is recommended for patients with CD4 count <200 cells/mcL.
T-cell counts should be appropriately interpreted in context of the clinical presentation and other immunological parameters and relevant laboratory test results.
For serial monitoring of T-cell numbers it is recommended that the patient be evaluated at the same time of the day to account for diurnal variation.
For follow-up of infants identified by newborn screening for severe combined immunodeficiency (SCID) and severe T-cell lymphopenia, SCID should be considered as a potential diagnosis in infants with <300 autologous CD3 T cells/mcL. Infants with 300 to 1,500 autologous CD3 T cells/mcL may have leaky SCID, Omenn syndrome, or variant SCID, depending on other clinical and molecular features.
T-cell lymphopenia in infants identified by newborn screening for SCID is defined as autologous CD3T cells < or =1,500 cells/mcL.
This assay should not be used for diagnosing T-lymphocytic malignancies or evaluation of T-cell lymphocytosis of unknown etiology, though the latter may be identified through this assay in a screening assessment. In such cases, LCMS / Leukemia/Lymphoma Immunophenotyping by Flow Cytometry will be recommended, which includes a hematopathology review.
Also, when diagnostically assessing lymphocyte subsets (quantitatively) in any of the above clinical contexts, it may be more useful to order the T-cell, B-cell, and natural killer TBNK cell quantitation assay rather than the T-cell subset quantitation alone, as it excludes B-and natural killer-cell counts.
The appropriate age-related reference values will be provided on the report.
1. 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
2. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009 May 21;113(21):5134-5143
3. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411
4. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med 1997;59:42-50
5. 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 Acquir Immune Defic Syndr 1990;3(2):144-151
6. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516
7. US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available from URL: http://aidsinfo.nih.gov/guidelines
8. Thompson MA, Aberg JA, Hoy JF, et al: Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA Panel. JAMA 2012;308:387-402