Rebecca McHugh | PubMed Health

PubMed2003

Neonates support lymphopenia-induced proliferation.

T cells expand without intentional antigen stimulation when transferred into adult lymphopenic environments. In this study, we show that the physiologic lymphopenic environment existing in neonatal mice also supports CD4 T cell proliferation. Strikingly, naive CD4 T cells that proliferate within neonates acquire the phenotypic and functional characteristics of memory cells. Such proliferation is inhibited by the presence of both memory and naive CD4 T cells, is enhanced by 3-day thymectomy, is independent of IL-7, and requires a class II MHC-TCR interaction and a CD28-mediated signal. CD44(bright) CD4 T cells in neonates have a wide repertoire as judged by the distribution of Vbeta expression. Thus, lymphopenia-induced T cell proliferation is a physiologic process that occurs during the early postnatal period.

Animals↗

PubMed2002

Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node.

The major histocompatibility complex (MHC)-dependent presentation of processed tissue-specific self-antigens can contribute to either peripheral (extrathymic) tolerance or the differentiation of autoreactive T cells. Here, we have studied the MHC class II molecule presentation of gastric parietal cell (PC)-specific H(+)/K(+)-ATPase, which induces a destructive autoimmune gastritis in BALB/c mice lacking CD4(+) CD25(+) regulatory T cells. Immunofluorescence microscopy showed physical association of CD11c(+) dendritic cells (DCs) with PCs in the gastric mucosa. H(+)/K(+)-ATPase protein was found within vesicular compartments of a few CD11c(+) DCs only in the draining gastric lymph node (LN) and these antigen-containing DCs increased markedly in number with the onset of tissue destruction in autoimmune animals. Both CD8alpha(hi) and CD8alpha(lo) gastric DCs, but not peripheral or mesenteric DCs, showed evidence of constitutive in vivo processing and presentation of H(+)/K(+)-ATPase. These data provide direct support for a widely held model of local tissue antigen uptake and trafficking by DCs in normal animals and demonstrate that DCs in the draining LN can present a tissue-specific self-antigen under noninflammatory conditions without fully deleting autoreactive T cells or inducing active autoimmunity.

Animals↗