Population studies showed that there are differences in T-lymphocytes subpopulation of normal children in different regions, and reference values in an area might be different from another. This study compared the values in our population with CDC and WHO reference values. Blood samples from 279 healthy, HIV-negative children 12 years of age were analysed for complete blood count, CD3+, CD4+, CD8+ counts and percentages. Except for CD8%, mean values for all parameters measured significantly decreased with age. CD4+ counts were higher in females than males, . Using the WHO criteria, 15.9% of subjects had low total lymphocyte count and 20.6% had low CD4 count. Children 3 years had median CD4% lower than WHO normal values. Our median CD4+ counts correlated with CDC values. Values used by WHO in infants are higher than ours. We suggest that our children be assessed using CDC reference values which correlate with ours. 1. Introduction The mature T-lymphocytes are defined by the presence of CD3, and either CD4+ or CD8+ unit antigens [1]. The CD4+ antigen-bearing T-lymphocyte subset also known as the T-helper cells has become popular since the advent of the Human Immunodeficiency Virus (HIV) infection. These T-lymphocytes are the primary targets of the HIV infection because the CD4+ antigen is the primary binding site of the HIV [2–4]. CD4+T cells serve as both essential regulators and effectors of the immune response; infection with HIV induces a progressive loss of these cells [5]. Profound decline of these cells underlies the immunodeficiency that results in Acquired Immunodeficiency Syndrome (AIDS) [2] The CD4+ T-cell count is the standard for assessing the immunologic progression of the disease, determination of need to commence antiretroviral (ARV) treatment, chemoprophylaxis for opportunistic infections, and for monitoring or modifying antiretroviral treatment [6, 7]. An adult individual has about 3000 lymphocytes per mm [3] in the peripheral blood with 70%–80% being T-lymphocytes and 65% of these T-lymphocytes bear CD4+ antigens [8, 9]. In children, the number of circulating T-cells increases from mid-gestation until the infant is about 6 months. This peak is followed by a gradual decline throughout childhood until adult levels are reached by late childhood [10]. As a result of the age-related changes in the absolute lymphocyte numbers and thus CD4+ count, the Centers for Disease Control and Prevention (CDC) in classifying children into immune categories using CD4+, produced a system based on specific age groups [11]. The World Health Organization
References
[1]
E. L. Reinherz and S. F. Scholssman, “Regulation of the immune response inducer and suppressor T lymphocyte subsets in human beings,” The New England Journal of Medicine, vol. 303, no. 7, pp. 370–373, 1980.
[2]
E. Robey and R. Axel, “CD4: collaborator in immune recognition and HIV infection,” Cell, vol. 60, no. 5, pp. 697–700, 1990.
[3]
J. L. Fahey, H. Prince, M. Weaver, et al., “Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders,” American Journal of Medicine, vol. 76, no. 1, pp. 95–100, 1984.
[4]
A. S. Fauci, A. M. Macher, D. L. Longo, et al., “Acquired immunodeficiency syndrome epidemiologic, clinical, immunologic, and therapeutic considerations,” Annals of Internal Medicine, vol. 100, no. 1, pp. 92–106, 1984.
[5]
H. Mohri, A. S. Perelson, K. Tung, et al., “Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy,” Journal of Experimental Medicine, vol. 194, no. 9, pp. 1277–1287, 2001.
[6]
“Guidelines for the use of antiretroviral agents in Pediatric HIV infection,” 2001, http://www.hivcommission-la.info/2001_guidelines.pdf.
[7]
United States Public Health Service (USPHS)/Infectious Disease Society of America (IDSA), “Guidelines for the prevention of opportunistic infections in HIV infected persons,” 2001.
[8]
I. Mota, “Tissue and cells of the immune system,” in Fundamentals of Immunology, D. G. Bier and W. Dias da Silva, Eds., pp. 1–34, Springer, London, UK, 1986.
[9]
C. Terhost, A. Van Agthovern, E. Reinherz, and S. Scholssman, “Biochemical analysis of human T-lymphocytes differentiation antigens T4 and T5,” Science, vol. 209, no. 4455, pp. 520–521, 1980.
[10]
T. Denny, R. Yogev, R. Gelman, et al., “Lymphocyte subsets in healthy children during the first 5 years of life,” Journal of the American Medical Association, vol. 267, no. 11, pp. 1484–1488, 1992.
[11]
Centers for Disease Control and Prevention, “1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age,” Morbidity and Mortality Weekly Report, vol. 43, no. RR-12, pp. 1–12, 1994.
[12]
World Health Organization, WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-Related Disease in Adults and Children, Geneva, Switzerland, 2006.
[13]
S. Smith and A. J. Melvin, “Normal development and physiology of the immune system,” in Handbook of Pediatric HIV Care, S. L. Zeichner and J. S. Read, Eds., pp. 1–22, Lippincott Williams and Wilkins, Baltimore, Md, USA, 9th edition, 1999.
[14]
X. Anglaret, S. Diagbouga, E. Mortier, et al., “CD4+ T-lymphocyte counts in HIV infection: are European standards applicable to African patients?” Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, vol. 14, no. 4, pp. 361–367, 1997.
[15]
J. Embree, J. Bwayo, N. Nagelkerke, et al., “Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi,” Pediatric Infectious Disease Journal, vol. 20, no. 4, pp. 397–403, 2001.
[16]
M. O. Njoku, N. D. Sirisena, J. A. Idoko, and D. Jelpe, “CD4+ T-lymphocyte counts in patients with human immunodeficiency virus type 1 (HIV-1) and healthy population in Jos, Nigeria,” The Nigerian Postgraduate Medical Journal, vol. 10, no. 3, pp. 135–139, 2003.
[17]
R. A. Audu, E. O. Idigbe, A. S. Akanmu, et al., “Values of CD4+ T lymphocyte in apparently healthy individuals in Lagos, Nigeria,” European Journal of Scientific Research, vol. 16, no. 2, pp. 168–173, 2007.
[18]
A. S. Akanmu, I. Akinsete, A. O. Eshofonie, A. O. Davies, and C. C. Okany, “Absolute lymphocyte count as surrogate for CD4+ cell count in monitoring response to antiretroviral therapy,” The Nigerian Postgraduate Medical Journal, vol. 8, no. 3, pp. 105–111, 2001.
[19]
E. S. Lugada, J. Mermin, F. Kaharuza, et al., “Population-based hematologic and immunologic reference values for a healthy ugandan population,” Clinical and Diagnostic Laboratory Immunology, vol. 11, no. 1, pp. 29–34, 2004.
[20]
G. M. Kam, W. L. Leung, K. H. Wong, S. S. Lee, M. Y. Hung, and M. Y. Kwok, “Maturational changes in peripheral lymphocyte subsets pertinent to monitoring human immunodeficiency virus-infected Chinese pediatric patients,” Clinical and Diagnostic Laboratory Immunology, vol. 8, no. 5, pp. 926–931, 2001.
[21]
HIV Paediatric Prognostic Markers Collaborative Study, “Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data,” The Lancet, vol. 366, pp. 1868–1874, 2005.
[22]
European Collaborative Study, “Are there gender and race differences in cellular immunity patterns over age in infected and uninfected children born to HIV-infected women?” Journal of Acquired Immune Deficiency Syndromes, vol. 33, no. 5, pp. 635–641, 2003.
[23]
B. Lee, H. Yap, and F. Chew, “Age- and sex-related changes in lymphocyte subpopulations of healthy Asian subjects: from birth to adulthood,” Cytometry, vol. 26, no. 1, pp. 8–15, 1996.
[24]
J. A. Bartlett, A. R. Goldklang, S. J. Schleifer, and S. E. Keller, “Immune function in healthy inner-city children,” Clinical and Diagnostic Laboratory Immunology, vol. 8, no. 4, pp. 740–746, 2001.
[25]
I. M. Lisse, P. Aaby, H. Whittle, H. Jensen, M. Engelmann, and L. B. Christensen, “T-lymphocyte subsets in West African children: impact of age, sex, and season,” Journal of Pediatrics, vol. 130, no. 1, pp. 77–85, 1997.
[26]
W. T. Shearer, H. M. Rosenblatt, R. S. Gelman, et al., “Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study,” Journal of Allergy and Clinical Immunology, vol. 112, no. 5, pp. 973–980, 2003.
[27]
Z. Ndhlovu, J. J. Ryon, D. E. Griffin, M. Monze, F. Kasolo, and W. J. Moss, “CD4+ and CD8+ T-lymphocyte subsets in Zambian children,” Journal of Tropical Pediatrics, vol. 50, no. 2, pp. 94–97, 2004.
[28]
J. Embree, J. Bwayo, N. Nagelkerke, et al., “Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi,” Pediatric Infectious Disease Journal, vol. 20, no. 4, pp. 397–403, 2001.
[29]
F. Rouet, A. Inwoley, D. K. Ekouevi, et al., “CD4 percentages and total lymphocyte counts as early surrogate markers for pediatric HIV-1 infection in resource-limited settings,” Journal of Tropical Pediatrics, vol. 52, no. 5, pp. 346–354, 2006.
[30]
L. S. Zijenah, D. A. Ktzenstein, K. J. Nathoo, et al., “T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years,” Journal of Translational Medicine, vol. 3, article 6, 2005.
[31]
N. Mansoor, B. Abel, T. J. Scriba, et al., “Significantly skewed memory CD8+ T cell subsets in HIV-1 infected infants during the first year of life,” Clinical Immunology, vol. 130, no. 3, pp. 280–289, 2009.