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Chapter 10:
Chapter 10:
Virginity
Naive T Cells
Recent studies identified fibroblastic reticular cells
in secondary lymphoid organs as essential source
of IL-7 and the CCR7 ligand CCL19.146 High expression of CCR7 and CD62L on naive T cells ensures
their homing to LN and, at the same time, enables
their IL-7-mediated survival. Under homeostatic
conditions, a stable population size of naive T cells
can thereby be maintained. The transcription factor
FoxO1 has been identified as important regulator
for the expression of CCR7, CD62L, and the chain
of the IL-7 receptor (CD127) on naive T cells. FoxO1deficient mice fail to home to secondary lymphoid
organs and show only very low levels of CD127,
which, in turn, leads to a decrease of naive T cells in
these mice.147 On robust activation, naive T cells undergo a process of expansion and differentiate into
effector cells with potent pathogen-eliminating
functions.148 A great proportion of effector cells dies
off within a few weeks, but few cells are selected to
enter the memory pool according to their capacity
to access and use of survival signals.
Memory T Cells.
Two types of CD45RO+ memory T cells can be generated: central memory and effector memory T cells.
(Central and effector memory T cells are discussed
in detail in the online edition.)
Central Memory T Cells.
Similar to naive T cells, long-lived central memory
T cells express the lymph node homing receptors
CD62L and CCR7, which allow their circulation
through peripheral blood and secondary lymphoid
organs. They are responsible for secondary or longterm responses to antigen and might be involved in
long-term maintenance of effector memory cells.149
The pool of memory T cells increases gradually with
age at the expense of their naive counterparts. In
contrast to naive T cells, memory T cells undergo
cell division within an interval of 23 weeks, which
is balanced by an almost equivalent number of cell
death.150 The homeostatic expansion and survival of
central memory T cells crucially depend on the responsiveness to IL-7 and IL-15, mediated via surface
expression of CD127 (IL7R) and CD122 (IL-15R),
respectively.151 Central memory T cells exhibit only
modest effector functions, but, upon rechallenge
with a given antigen, they can develop into effector
T cells.152
It appears that the strength of the antigenic signal
determines the ultimate fate of a naive T cell, as
robust TCR signaling may result in the generation
of effector memory T cells.149 Contrary to central
memory T cells, effector memory cells are excluded
from secondary lymphoid organs, but home to peripheral tissues and are responsible for immediate
protection against challenge. Following the peak of
the immune response, most of these cells disappear
from the blood and central memory T cells appear
instead. It seems that effector memory cells represent a transitory population rather than a distinct
cell type, ending with the development of central
memory T cells.153 Conversely, central memory T
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Chapter 10:
host responses (see Section CD1-Dependent Antigen Presentation). On antigenic stimulation, NKT
cells produce large quantities of cytokines, particularly IL-4 and IL-10, and can use them to suppress
Th1 responses. The biologic relevance of these in vitro data can be deduced from the observation that
depletion of NKT cells can aggravate and accelerate
Th1-mediated autoimmune diseases in mice, such
as insulin-dependent diabetes, multiple sclerosis,
and inflammatory bowel disease.180
Chapter 10:
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Chapter 10: