Functionally active CD8alphabeta+ TCRgammadelta intestinal intraepithelial lymphocytes in athymic nu/nu mice.
Murine intestinal intraepithelial lymphocytes (IEL) encompass a high proportion of TCRgammadelta cells. A vast majority of these TCRgammadelta IEL express CD8alpha, but not CD8beta (CD8alphaalpha homodimer), and are considered to develop in intestinal epithelial layers independently of a functional thymus. Here we show that TCRgammadelta cells expressing both CD8alpha and CD8beta (CD8alphabeta heterodimer) appear in athymic nu/nu mice, although their appearance is random. The IEL comprising CD8alphabeta(+) TCRgammadelta cells expressed pronounced cytolytic and IFN-gamma-producing activities after TCRgammadelta ligation, which were markedly stronger than activities of IEL lacking CD8alphabeta(+) TCRgammadelta cells. Purified CD8alphabeta(+) TCRgammadelta cells expressed strong cytolytic activities and produced large quantities of IFN-gamma after TCR engagement. CD8alphabeta(+) TCRgammadelta cells were also identified among IEL from euthymic C57BL/6 mice, although their abundance varied among individual animals. However, cytolytic and IFN-gamma-producing activities in euthymic C57BL/6 mice were markedly lower than those in athymic nu/nu mice. Our findings suggest that CD8alphabeta(+) TCRgammadelta cells can develop in the intestine independently of a functional thymus/thymic epithelial cells and that they perform biological functions in situ.
Emoto
Yoshiko
Y
Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstrasse 21/22,10117 Berlin, Germany. emoto@mpiib-berlin.mpg.de
Emoto
Masashi
M
Miyamoto
Mamiko
M
Yoshizawa
Izumi
I
Kaufmann
Stefan H E
SH
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004848:Epithelium / Q000276:immunology*; D005434:Flow Cytometry; D007118:Immunoassay; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma