Biology Reference
In-Depth Information
fail to undergo HP and erode in number in the absence of MHC class I, also retain
the ability to respond to dendritic cell-mediated antigenic stimulation for at least
1 week after transfer into TAP(/) mice
[82]
. Resting memory CD4() cells are
dependent on signals from contact with IL-7 and IL-15, but not MHC class II, for
their survival and intermittent HP
[83]
.
Thymus and oncostatin M (OM)-dependent HP extrathymic pathways of T cells
show how the division of labor between primary and secondary lymphoid organs
influences the repertoire and homeostasis of T lymphocytes
[84]
. CD8() T cells
express thymic stromal lymphopoietin (TSLP) receptors, and TSLP activates both
STAT5 and Akt and induces Bcl-2 in these cells. Correspondingly, TSLP increases
CD8() T-cell survival
in vitro
as well as in wild-type and T-depleted mice
in vivo
,
without altering the HP of these cells. Moreover, TSLP can maintain CD8() T cells
even in the absence of IL-7
[85]
.
Recent work has shown that two members of the gamma c family of CTKs, IL-7
and IL-15, govern homeostasis of memory T cells. It appears that the two types of
memory cells do not display identical homeostatic requirements. For antigen-specific
memory CD8 T cells, IL-7 is primarily important for survival, whereas IL-15 is
crucial for their background proliferation. For memory CD4 T cells, IL-7 has an
important role, whereas the influence of IL-15 is still unclear
[86]
. The activation
of STAT5 is the primary mechanism underlying both IL-7- and IL-15-dependent HP
of naïve and memory CD8() T cells and IL-2-dependent development of CD4()
CD25() regulatory T cells (Tregs)
[87]
. There are distinct functions for IL-7 and
IL-15 in T lymphocyte development and homeostasis, and stringent regulation of
these processes by suppressor of cytokine signaling-1 (SOCS1)
[88]
.
Dividing HP memory T cells were present in both lymphoid and nonlymphoid
tissues. However, the bone marrow was the preferred site for proliferation and con-
tained a major pool of the most actively dividing memory CD8 T cells. Adoptive
transfer studies indicated that memory cells migrated through the bone marrow and
divided there preferentially
[89]
. Homeostatic expansion permits T cells to reenter
the thymus and deliver antigen in a tolerogenic fashion
[90]
.
In sublethally irradiated lymphopenic mice, HP T lymphocytes were found to
arise in neonatal lymphopenia (CD8 T cells)
[91]
, which inhibited melanoma
and colon carcinoma growth; this protection was effective even against established
tumors (T cells making IFN)
[92]
. HP T cells generated autoimmunity (IL-21 reg-
ulated T cell turnover)
[93]
. HP T cells appeared 14 days after burn injury. These
cells were CD8 CD44 IL-7R T cells, which induced enhanced allogeneic
skin graft rejection in unburned recipient mice. Treatment with GC abolished both
the late homeostatic accumulation of CD8 memory-like T cells and enhanced
the pro-inflammatory CD8 T-cell response, but not the late enhanced CD8
anti-inflammatory response
[94]
.
HP T cells transformed chronic rejection to acute rejection of a single MHC class
II-mismatched kidney allograft. Such T cells consistently caused reliable rejec-
tion even when bona fide memory T cells could not. These functional changes are
long-lasting and not restricted to the acute phase of HP
[95]
. HP cells obtained from
T-cell knockout (KO) mice mounted relatively normal acute CD8 T-cell responses to
