Sm. Martin et al., Development of intestinal intraepithelial lymphocytes, NK cells, and NK 1.1(+) T cells in CD45-deficient mice, J IMMUNOL, 166(10), 2001, pp. 6066-6073
The transmembrane protein tyrosine phosphatase CD45 is differentially requi
red for the development and function of B, T, and NK cells, with mice parti
ally deficient for CD45 having a significant inhibition of T cell, but not
NK or B cell, development. CD45-mediated signaling has also been implicated
in the development of intrathymic, but not extrathymic, intestinal intraep
ithelial T lymphocytes (iIELs) in the CD45ex6(-/-) mouse. As NK1.1(+) CD3() (NK-T) cells can also develop through extrathymic pathways, we have inves
tigated the role of CD45 in NK-T cell development. In mice with a complete
absence of CD45 expression (CD45ex9(-/-)) the NK-T cell population was main
tained in the iIEL compartment, but not in the spleen. Functionally, CD45-d
eficient NK-T cells were unable to secrete IL-4 in response to TCR-mediated
signals, a phenotype similar to that of CD45-deficient iIELs, in which in
vitro cytokine production was dramatically reduced. Using the CD45ex9(-/-)
mouse strain, we have also demonstrated that only one distinct population o
f NK-T cells (CD8(+)) appears to develop normally in the absence of CD45. I
nterestingly, although an increase in cytotoxic NK cells is seen in the abs
ence of CD45, these NK calls are functionally unable to secrete IFN-gamma.
In the absence of CD45, a significant population of extrathymically derived
CD8 alpha alpha (+) iIELs is also maintained. These results demonstrate th
at in contrast to conventional T cells, CD45 is not required during the dev
elopment of CD8(+) NK-T cells, NK cells, or CD8 alpha alpha (+) iIELs, but
is essential for TCR-mediated function and cytokine production.