CDR3和TCR-gd T細胞促使受MHC-II限制的CD4+ T細胞亞羣經由發育過程得到IL-4分泌潛能進而調控IgE的產生
Other Title
CDR3- and TCR-gd T cell-dependent developmental acquisition of IL-4 inducibility in a subset of MHC-II-restricted CD4+ T cells regulates serum IgE levels
Date Issued
2005
Date
2005
Author(s)
Chen, Yi-Ting
DOI
en-US
Abstract
CD1d-restricted NKT cells respond to TCR-stimulation by prompt IL-4 production and were originally thought to play a major role in the initiation of IgE response. NK1-CD44lowCD4+CD8- thymocytes were also capable of TCR-stimulated prompt IL-4 inducibility in all common mouse strains examined. The property of IL-4 inducibility by these NK1-CD44lowCD4+CD8- thymocytes was found primarily in Va3.2+ and Vb2/7/8+ cells. Unlike NKT cells, the development of IL-4 inducibility+ NK1-CD44lowCD4+CD8- thymocytes was b2m-, CD1d-, and p59fyn-independent. NK1-CD44lowCD4+CD8- thymocytes also produced IL-5, IL-10, and IL-13, but very low levels of IFN-g in response to TCR stimulation. The IL-4 inducibility+ NK1-CD44lowCD4+CD8- thymocytes expressed highly diverse CDR3 in both TCR a and b chains. Va3.2 and Vb8 CDR3 from single IL-4 mRNA+ and IL-4 mRNA- cells were subcloned into full-length Va3.2 and Vb8 transgene constructs, and injected into fertilized eggs to produce TCR transgenic mice. A “P”-series of 8 independent TCR transgenic lines (4 each of TCR-a and -b) were produced from Va3.2 and Vb8 cloned from 4 randomly selected IL-4-producing single NK1-CD44lowCD4+CD8- thymocytes. Another “N”-series of 6 independent TCR transgenic lines (3 each of TCR-a and -b) were produced from Va3.2 and Vb8 cloned from 3 randomly selected IL-4-non-producing single NK1-CD44lowCD4+CD8- thymocytes. Single TCR-a and -b transgenic mice were crossed to generate double TCR-ab transgenic mice. All P-series TCR-ab transgenic mice displayed elevated IL-4 inducibility in Va3.2+Vb8+ thymocytes and increased serum IgE levels. All N-series TCR-ab transgenic mice, on the other hand, expressed low or negligible IL-4 inducibility in Va3.2+Vb8+ thymocytes and had normal serum IgE levels. Positive selection of P3 TCR-ab transgenic T cells was MHC-II-, but not MHC-I- or CD1d-dependent. Positive selection was necessary but not sufficient in conferring IL-4 inducibility which was dependent on the presence of TCR-gd T cells. These results demonstrate 1) the existence of a MHC-II-restricted CD4+ T cell subset capable of prompt IL-4 inducibility; 2) the critical roles played by CDR3 of both TCR-a and -b chains and by TCR-gd T cells in the acquisition of IL-4 inducibility and elevated serum IgE levels; and 3) the likelihood for the IL-4 inducibility+ NK1-CD44lowCD4+CD8- T cells to participate in immune response to a relatively large number of antigens due to their highly diverse TCR repertoire.
Subjects
CD4 T cells
IL-4
thymus
repertoire development
Type
other