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T cells are major effector cells of the adaptive immune response from influencing antibody production to maintaining tolerance. The defining marker of the T cell is the T-cell receptor (TCR), and 2 distinct T-cell subsets have been characterized based on the structure of the TCR: TCRα/β and TCRγδ. The specificity of the TCRα/β T-cell repertoire is established during fetal development of the thymus, which develops at week 6 of gestation. Immature thymic cells develop from fetal liver cells and, after birth, from hematopoetic stem cells (HSCS) in the bone marrow. T cells develop from common lymphoid progenitor cells derived from HSCs within the thymus and undergo stages of differentiation, expressing 1 or both of the cytodifferentiation (CD) antigens CD4 and CD8. T cells expressing the α/β TCR are divided into various subsets based on surface CD antigens and function. CD4+ T cells, or helper T cells (TH), make up approximately 70% of T cells in the peripheral blood. TH cells recognize foreign antigens processed and presented in major histocompatibility complex (MHC) class II molecules and can be divided into additional subsets. TH1 CD4+ T cells produce interferon gamma (IFN-γ) and IL-2, favor antibody class switching to immunoglobulin (Ig) G2, and mediate protection against intracellular pathogens. TH2 CD4+ T cells produce IL-4, IL-13, and IL-5, favor class switching to IgG1 and IgE, and participate in atopic diseases and immunity against parasites. More recently, additional subsets of CD4+ T cells have been described that have effector functions against extracellular microbes: TH9 cells produce the anti-inflammatory cytokine IL-10 and are involved in the host defense against nematodes, whereas TH17 cells secrete IL-17, IL-21, and IL-22 and promote protective immunity against extracellular bacteria and fungi at mucosal surfaces. CD8+ cytotoxic T lymphocytes (CTLs) recognize endogenous proteins bound to MHC class I molecules, such as viral and tumor antigens, and mediate cytotoxicity by lysing altered or nonself cells. A third class of T cells (typically CD4+) with immune suppressive function are denoted as regulatory T cells (Treg) and can be identified (albeit with some exception) by the expression of the transcription facto FOXP3 (forkhead box P3). Treg cells are produced directly from the thymus (natural Treg) or induced within the periphery (induced Treg) and play major roles in mediating chronic inflammation, allergic disease, and autoimmunity.1


T-cell dysfunction in neonates has implications for a variety of responses and disease states. Infants are more susceptible to infectious agents, and according to the World Health Organization (WHO) estimates, approximately 2.5 million infants under the age of 1 die annually of infection. Infants are also less responsive to vaccination. In vaccinated infants, immunity wanes around 6–9 months after vaccination, and multiple booster shots are needed to maintain immunological memory.2 Historically, the function of neonatal T cells has been considered ...

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