Liipat group news: Regulatory T cells (T(regs)) may inhibit immunity against cancer.
Heier I, Hofgaard PO,
Brandtaeg P, Jahnsen FL, Karlsson M.
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Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour
growth in a mouse model of B cell lymphoma.
Clin Exp Immunol. 2008 May;152(2):381-7. Epub 2008 Mar
Regulatory T cells (T(regs)) may inhibit immunity against cancer.
Induction and expansion of T(regs) in the immunosuppressive
microenvironment created by a growing tumour appear to be one
of the mechanisms by which it can evade host defence. We studied
the impact of CD25+ T(regs) in a B cell lymphoma model in which
Rag2-/- mice received adoptive transfer of wild-type spleen cells
with or without CD25+ cells, and concurrently subcutaneous
inoculation of the B cell lymphoma cell line A20. We also examined
the effect of engaging the glucocorticoid-induced tumour necrosis
factor receptor (GITR) - an approach reported previously to abrogate
the suppressive effects of T(regs). Mice that received spleen cells
depleted of CD25+ T(regs) showed significantly slower tumour growth
and increased survival compared with mice that received unsorted
spleen cells. The T(reg)-depleted group also had significantly more
CD8+ T cells infiltrating the tumours and higher levels of serum
immunoglobulin G subclasses. The anti-GITR treatment had no significant
effect on tumour growth, survival or immunoglobulin production. In
the CD25-depleted group four of 10 mice developed clinical signs of
autoimmunity, in contrast to none in the non-depleted group. Forkhead
box P3+ T cells were found in tumour-draining lymph nodes in mice
in the CD25-depleted group, suggesting an in vivo induction or
expansion of rare transferred donor T(regs). Thus, our study showed
that removal of CD25+ T(regs) enhanced anti-tumour immunity against
local growth of a B cell lymphoma and that induction or expansion of
T(regs) could be one mechanism by which the growing tumour evades
immune surveillance.