Development and Maintenance of the Gut-Associated Lymphoid Tissue (Galt): the Roles of Enteric Bacteria and Viruses
Development and Maintenance of the Gut-Associated Lymphoid Tissue (GALT): The Roles of Enteric Bacteria and Viruses
JOHN J. CEBRA 0
SANGEETA BHARGAVA PERIWAL 0
GWEN LEE 0
FAN LEE 0
KHUSHROO E. SHROFF 0
0 Department of Biology, University of Pennsylvania , Philadelphia, PA 19104-6018 , USA
GALT can be subdivided into several compartments: (a) Peyer's patches (PP); (b) lamina propria (LP); and (c) intraepithelial leukocyte (IEL) spaces. The B-cell follicles of PP are quiescent in neonatal and germ-free (GF) adult mice. Germinal centers (GC), including slgA blasts, appear in the B follicles of formerly GF adult mice about 10-14 days after monoassociation with various gut commensal bacteria. The GC wax and wane over about a 3-week period, although the bacterial colonizers remain in the gut at high density. Neonatal mice, born of conventionally reared (CV), immunocompetent mothers, display GC reactions in PP postweaning, although pups of SCID mothers display precocious GC reactions at about 14 days of life. Normally, gut colonization of neonates with segmented filamentous bacteria (SFB) leads to explosive development of IgA plasmablasts in LP shortly after weaning. Commensal gut bacteria and the immunocompetency of mothers also appears to control the rate of accumulation of primary B cells from "virgin" B cells in neonates. Enteric reovirus infection by the oral route can cause the activation of CD8 T cells in the interfollicular regions of PP and the appearance of virus-specific precursor cytotoxic T lymphocytes (pCTL) in the IEL spaces. Such oral stimulation can also lead to "activation" of both CTL and natural killer (NK) cells in the IEL spaces. More normally, colonization of the gut with SFB also leads to similar activations of NK cells and "constitutively" cytotoxic T cells.
Enteric viruses; gut-associated lymphoid tissue (GALT); gut commensal bacteria; IgA responses in gut; intraepithelial leukocytes; Peyer's patches
INTRODUCTION
GALT includes both organized lymphoid
compartments, consisting of PP, regional lymphatics, and
mesenteric lymph nodes (MLN), and dispersed
lymphoid cells in the IEL spaces and the gut LP
(Owen
and Jones, 1974; Cerf-Bensussan and Guy-Grand,
1991)
. The PP consist of a single-layer cluster of
Bcell follicles, divided by T-cell-rich wedges, unevenly
distributed in the wall of the small intestine. A
specialized follicle-associated epithelium (FAE)
overlies these clusters, forming a relatively mucus-free
"dome" among the absorptive villi and their
interspersed crypts. Among the cells of FAE are
specialized M (microfold) cells, which actively pinocytose or
endocytose droplets and particles from the gut lumen
Owen and Jones, 1974). These M cells serve as
"afferent lymphatics" for PP, delivering antigens
(Ags) and pathogens to the underlying, organized
lymphoid tissue
(Wolf et al., 1981; Jones et al., 1994)
.
The B-cell follicles in PP of CV mammals are not
typically quiescent (primary), as in lymph nodes or
spleen, but rather display continuous GC reactions
and are chronically activated (secondary).
Presumably, these GC reactions are constantly driven by the
environmental Ags delivered via M cells. The GC in
PP of mice typically bind high levels of peanut
agglutinin (PNA--a marker for the B blasts) and
contain a preponderance of dividing, IgA-expressing
B blasts
(Lebman et al., 1987; Weinstein et al., 1991)
.
Surface IgD-bearing B cells (primary B cells) are
confined to the recirculating population comprising
the surrounding mantle zone.
Lymphocyte Recirculation from and to GALT
Among the B cells leaving PP via efferent lymphatics
are IgA B cells, generated and selected for survival
in GC
(Craig and Cebra, 1971; Lebman et al., 1987)
.
These pass through MLN, where some are maturing
to IgA plasma blasts (McWilliams et al., 1975).
Eventually, these IgA B cells are found in thoracic
duct lymph
(Pierce and Gowans, 1975)
and blood,
having developed a homing propensity to exit into
and accumulate in mucosal tissues via transit of small
venules
(Husband, 1982)
. Many of the IgA
plasmablasts generated in PP eventually accumulate and
secrete their IgA Abs in the gut LP.
At least one T-cell subset that can contribute to gut
immunity (CD8 CTL) can be generated by
Agstimulation in the interfollicular regions of PP
(London et al., 1987, 1990)
. Some of these emigrate to the
IEL spaces, where they selectively lodge and can
function as one subset of CTL among other NK and
CD8 T cells from other sources (Cuff et al., 1993).
Roles of IgA Abs and T Lymphocytes in GALT
Dimeric IgA Abs, produced locally by IgA plasma
cells in gut LP, are actively transported via poly
Igreceptors (pig-R) into and through gut epithelial cells,
especially crypt cells
(Mostov et al., 1980)
. During
exocytosis into crypt and gut lumen, the pIg-R is
cleaved and a portion (secretory component) remains
complexed to IgA dimer. This "secretory" IgA can
function as a "blocking" or "neutralizing" Ab in the
gut l (...truncated)