Pediatric reference values for the peripheral T-cell compartment

Abstract

Immunophenotyping of blood lymphocyte subpopulations is an important tool in the diagnosis of immunological and hematological diseases. Pediatric age-matched reference values have been determined for the major lymphocyte populations, but reliable reference values for the more recently described T-lymphocyte subpopulations, like different types of memory T-lymphocytes, recent thymic emigrants, regulatory T-cells and CXCR5 + helper-Tlymphocytes, are not sufficiently available yet. We determined reference values for the absolute and relative sizes of T-lymphocyte subpopulations in healthy children using the lysed whole blood method, which is most often used in diagnostic procedures. When the absolute numbers of some or all T-lymphocyte subpopulations fall outside these reference ranges, this may indicate disease. The reference values show the course of T-lymphocyte development in healthy children. Absolute T-lymphocyte numbers increase 1.4-fold during the first months of life and after 9-15 months they decrease threefold to adult values; this is mainly caused by the expansion of recent thymic emigrants and naive cells. Helper and cytotoxic T-lymphocytes show the same pattern. Regulatory T-cells increase in the first five months of life and then gradually decrease to adult values, although the absolute numbers remain small. The relative number of CXCR5 + cells within the CD4 + CD45RO + T lymphocytes increases during the first six months of life and then remains more or less stable around 20%.and negative control of immune responses. Annu Rev Immunol. 2004;22:531-62. 11 Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC. Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. 13 van Gent R, van Tilburg CM, Nibbelke EE et al. Refined characterization and reference values of the pediatric T-and B-cell compartments. Clin Immunol. 2009 Oct;133:95-107. 14 Reimann KA, Chernoff M, Wilkening CL, Nickerson CE, Landay AL. Preservation of lymphocyte immunophenotype and proliferative responses in cryopreserved peripheral blood mononuclear cells from human immunodeficiency virus type 1-infected donors: implications for multicenter clinical trials. The ACTG Immunology Advanced Technology Laboratories. Clin Diagn Lab Immunol. 2000 May;7:352-9. 15 Hokland P, Heron I. Analysis of the lymphocyte distribution during Isopaque-Ficoll isolation of mononuclear cells from human peripheral blood. J Immunol Methods. 1980;32:31-9. 16 Saule P, Trauet J, Dutriez V, Lekeux V, Dessaint JP, Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech Ageing Dev. 2006 Mar;127:274-81. 17 Kraan J, Gratama JW, Keeney M, D'Hautcourt JL. Setting up and calibration of a flow cytometer for multicolor immunophenotyping.

Extended immunophenotyping reference values in a healthy pediatric population

“…Although RVs for the most common lymphocyte subpopulations have been reported in pediatric patients , these data are not valid as general RVs for the diagnosis of hematological and immunological disorders for several reasons: (i) limited number of blood samples from children aged less than 2 years, (ii) 10th and 90th percentiles are unavailable for all cell populations, (iii) data are missing for many of the recently defined memory T cell populations, and (iv) incomplete data on reagents, staining protocols, instrument settings, and acquisition and analysis procedures . The lack of consensus in the stratification by age and the criteria for including healthy donors are factors precluding use of the available RVs.…”

EuroFlow Standardized Approach to Diagnostic Immunopheneotyping of Severe PID in Newborns and Young Children

“…There have been multiple initiatives for establishing comprehensive and detailed reference values of human lymphocyte subsets in children by several groups (34)(35)(36). These studies were done by using two to four color flow cytometry.…”

Primary Immunodeficiency Associated With Chromosomal Aberration – An Esid Survey

“…Clinical characteristics and identified immunological abnormalities were reported. Age-matched reference values were used for interpretation of immunoglobulin levels and lymphocyte subpopulation counts; values below the age-matched reference values were scored as 'low' [29][30][31]. For the interpretation of the vaccine responses (i.e.…”