Superantigens Are Presented by and Activate Thymocytes from Infants

Abstract

A high percentage of human fetal and postnatal thymocytes express MHC class II molecules. This raises the possibility that human thymocytes in early life are able to present peptides to other immature T cells and thereby initiate thymic selection of these cells. Here we address this question by exposing newly harvested infant thymocytes to superantigen (Sag) which binds to the T-cell receptor and to MHC class II chains outside the peptide binding groove. The results show that the thymocytes are able to present Sag and to be activated to proliferation as well as apoptosis by Sag presented by other thymocytes. The absence of responses to Sag with mutations in class II binding sites showed that class II molecules were necessary for the responses, and very low expression of class II molecules on CD4–8– cells indicates that the demonstrated T-cell/T-cell interactions are confined to T-cell receptor-positive CD4+8+, CD4+8–, and CD4–8+ cells. These latter subsets were shown to be able to present Sag to each other. These findings suggest that class II+ thymocytes may participate in the selection of self-restricted T cells during a critical period in the shaping of the human immune system.

An Alternate Pathway for CD4 T Cell Development: Thymocyte-Expressed MHC Class II Selects a Distinct T Cell Population

“…A considerable percentage (30%-50%) of human fetal and postnatal thymocytes express MHC class II molecules (Gilhus and Matre, 1983;Marinova et al, 2001;Park et al, 1992;Thulesen et al, 1999). Under normal conditions, it is likely that human thymocytes can induce maturation of neighboring thymocytes.…”

“…In contrast, human CD4 T cells are known to express CIITA and MHC class II upon activation. In addition, several groups have reported that a significant proportion of human fetal and postnatal thymocytes express MHC class II molecules (Gilhus and Matre, 1983;Marinova et al, 2001;Park et al, 1992;Thulesen et al, 1999). In a thymic reaggregate culture system in vitro (Choi et al, 1997), MHC class IIexpressing human DP thymocytes seem to play a role for their own positive selection through T-T interaction.…”

The SLAM-Associated Protein Signaling Pathway Is Required for Development of CD4+ T Cells Selected by Homotypic Thymocyte Interaction

“…These data, together with another report showing that mice with T-CD4 T cells are protected from experimental autoimmune encephalomyelitis (EAE) , suggest that T-CD4 T cells could have an important immunoregulatory role. Although mice do not naturally express MHC class II in thymocytes, a substantial percentage of human fetal and neonatal thymocytes express MHC class II (Marinova et al, 2001;Park et al, 1992;Thulesen et al, 1999), and several observations support the presence of two selection pathways in humans (Godthelp et al, 2000;Klein et al, 1995;Markert et al, 2004).…”

Superantigen Presentation by Human Retinal Pigment Epithelial Cells to T Cells is Dependent on CD2–CD58 and CD18–CD54 Molecule Interactions

“…3 Hthymidine incorporation was measured by liquid scintillation counting. In some experiments a mutant SEA was used: SEA-F47A/D227A (PharmaciaUpjohn, Lund, Sweden) with mutations in both MHC class II binding sites [M()] (Newton et al, 1996;Thulesen et al, 1999).…”