Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors
Autor: | Christian E. Demeure, Dae Gyoo Byun, Yusei Ohshima, Liang Peng Yang, Marika Sarfati, Uno Shu, Guy Delespesse |
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Rok vydání: | 1998 |
Předmět: |
Adult
CD4-Positive T-Lymphocytes General Veterinary General Immunology and Microbiology T cell Infant Newborn Public Health Environmental and Occupational Health CD28 Priming (immunology) CD8-Positive T-Lymphocytes Th1 Cells Biology Interleukin 21 Th2 Cells Infectious Diseases medicine.anatomical_structure Immunology Interleukin 12 medicine Humans Molecular Medicine Cytotoxic T cell IL-2 receptor CD8 |
Zdroj: | Vaccine. 16:1415-1419 |
ISSN: | 0264-410X |
DOI: | 10.1016/s0264-410x(98)00101-7 |
Popis: | The increased susceptibility of neonates to infections has been ascribed to the immaturity of their immune system. More particularly, T cell-dependent responses were shown to be biased towards a Th2 phenotype. Our studies on the in vitro maturation of umbilical cord blood T cells suggest that the Th2 bias of neonatal response cannot be simply ascribed to intrinsic properties of neonatal T cells. Phenotypically, neonatal CD4 + T cells are more immature than their adult CD45RO − /RA + naive counterparts and they contain a subset (10–20%) of CD45RO − /RA + CD31 − cells which is very low in adults and displays some unique functional features. The activation and maturation of neonatal CD4 + T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12. Activation of adult as well as neonatal CD4+ T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine, i.e. IL-2. In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFNγ and TNFβ) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells. The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by an autocrine pathway. The ability of IL-12 to prime neonatal CD4 + T cells for increased production of IL-4 (in addition to IFNγ) is observed only when CD28 cosignal is minimal. Under optimal activation conditions (i.e. with anti-CD3/B7.1 or allogenic dendritic cells) the response and the maturation of neonatal and adult naive T cells are similar. Thus the Th2 bias of neonatal immune response cannot be simply ascribed to obvious intrinsic T cell defect but rather to particular conditions of Ag presentation at priming. Unlike CD4 + T cells, neonatal CD8 + T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers. Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-1 infection in vitro. |
Databáze: | OpenAIRE |
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