N. Seo et Y. Tokura, Downregulation of innate and acquired antitumor immunity by bystander gamma delta and alpha beta T lymphocytes with Th2 or Tr1 cytokine profiles, J INTERF CY, 19(6), 1999, pp. 555-561
It has been thought that natural killer (NK) cells appearing early in tumor
lesions play a pivotal role in the innate immunity against tumor cells. Al
though NK cells serve as the first tumoricidal effector cells, they subsequ
ently promote a shift in effecters from themselves to tumor-specific cytoto
xic T lymphocytes (CTLs) that mediate the acquired immunity. The mechanism
of this shift has not been fully elucidated, however, NK cell-derived T hel
per (Th) 1 cytokines such as interferon (IFN)-gamma seem to play a key role
. Another NK-lineage, termed natural killer T (NK T) cells, may also partic
ipate in the innate period when they acquire the ability to secrete Th1 cyt
okines. Interleukin-4 (IL-4) and IL-10, belonging to Th2, and transforming
growth factor-beta (TGF-beta), belonging to T regulatory (Tr) 1 cytokines,
are known to suppress the development of NK, NK T cells, as well as CTLs an
d to block Th0 cell differentiation to Th1 cells, suggesting that tumor cel
ls can evade the innate and acquired immunity by virtue of cells producing
these inhibitory cytokines. In early tumor lesions of murine B16 melanoma,
gamma delta T and alpha beta intermediate ((int))T cells that co-infiltrate
with NK and NK T cells can produce Th2 cytokines and inhibit the innate im
munity. In MM2 mammary tumor-bearing mice, gamma delta T cells appearing bo
th lesionally and systemically secrete Tr1-type cytokines and depress the a
cquired immunity. These Th2- or Tr1-type gamma delta T and alpha beta(int)
T cells downregulate the tumoricidal cells by means of both their secreted
cytokines and express major histocompatibility complex (MHC) class I molecu
les.