T Cell Development in the Fetus and Neonate

Abstract

INTRODUCTION Properties of T CellsT lymphocytes (T cells) playa central role in the immune response acting both to mediate specific immune functions and to modulate the function of all other aspects of the immune system. T cells mediate these effects both through direct cell-cell interactions and through the production of soluble mediators known as lymphokines.T cells recognize antigen through a specific receptor, which is a heterodimeric structure similar to immunoglobulin1. Most T cells (-95%) express a T cell receptor (TCR) composed of an a and a /3 chain; these chains associate to form the antigen recognition portion of the TCR. The selective recognition of antigens is determined by variable portions of the molecules that are located in their amino-terminal half. The TCR associates on the cell surface with the pentameric CD3 complex, which links the TCR to other cellular components needed to mediate transduction of signals from the receptor to the cell interior2,3. A much smaller fraction (3-5%) of T cells express a TCR composed of a yand a ~ chain; in humans the fraction of T cells expressing the y~ form of the TCR in neonates was similar to that in adults in one study4 and less in another4 a . Most y~ TCR expressing T cells do not express either the CD4 or CD8 molecule. In contrast to T cells bearing the all TCR, the function of T cells bearing the y~ form of the TCR is not yet clear, although it has been suggested that they may playa role in defense against mycobacteria, in removal of damaged cells expressing heat shock proteins and in autoimmune diseaseS,Sa. Virtually all T cells bearing the a/3 TCR also express on their surface either the CD4 (T4) or the CD8 (T8) molecule. These molecules act with the TCR to endow the T cell with the capacity to recognize specific antigen 1,6,7.T cells recognize antigen in a way that is fundamentally different from the manner in which B cells (and immunoglobulin, which is the B cell antigen receptor) recognize antigen. Immunoglobulin binds to free antigen, often recognizing secondary or tertiary structure. T cells generally recognize relatively short (-8-9 amino acids) pep tides, derived by the processing of larger proteins, and only do so when the peptide is bound to a major histocompatibility (MHC) molecule (known as HLA antigens in humans). The CD4 and CDS molecules determine whether a T cell will recognize antigen bound to class II MHC molecules (HLA-D in man) or bound to class I MHC molecules (HLA-A, -B, and -C in man), respectively6. The corecognition of antigen in association with self MHC molecules is central to the role of T cells in self/non-self discrimination. Development of T Cells from Hematopoietic PrecursorsT cells are derived from hematopoietic precursors, which migrate to and colonize the human embryonic thymus at approximately S weeks of gestation8-10 . In the thymus, prothymocytes acquire the TCR and the CD3 complex and initially express on their surface both the CD4 and the CDS molecules; because they express both the CD4 and the CDS molecules these ...

In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults.

“…3). This supports previous studies showing offspring of healthy mothers contain only naive T cells incapable of producing these cytokines (36)(37)(38). In contrast, 24 and 17% of Kenyan infants produced detectable levels of SWAP-and BmA-induced IL-5, respectively, and 57 and 28% produced IFN-␥ in response to SWAP and BmA, respectively (Fig.…”

Innate defense regulator peptide synergizes with CpG ODN for enhanced innate intestinal immune responses in neonate piglets

“…The intestinal mucosa in newborns is significantly less colonized by immune cells than that in adults [1]. We therefore characterized the capacity of IN given CpG-HH2 to induce immune cell recruitment in the intestine and MLN of neonatal piglets.…”

“…It is believed that neonates exhibit functionally impaired antigen presentation, shorter lived and weaker antibody responses, a Th2-type immune response bias and a decreasing overall cell-mediated immune response if compared with adults [1][2][3].…”

Imaturidade imunológica fetal e neonatal: implicações na evolução clínica da infecção pelo HIV-1 em crianças

“…Entretanto, essas células são funcionalmente imaturas. Praticamente todos os linfócitos neonatais expressam a molécula CD38, um antígeno de superfície marcador de timócitos e inexistente em linfócitos maduros 33 . Ao contrário dos linfócitos adultos, dos quais 50% a 60% expressam o marcador de células de memória CD45RO, a quase totalidade dos linfócitos neonatais expressa CD45RA, um marcador de célu-las não-primadas 34 .…”