10 research outputs found
Involvement of Glucocorticoids in the Reorganization of the Amphibian Immune System at Metamorphosis
In recent years, integrative animal biologists and behavioral scientists have begun to understand
the complex interactions between the immune system and the neuroendocrine system.
Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-driven
changes in the immune system in a compressed time frame. In the South African clawed frog,
Xenopus laevis, the larval pattern of immunity is distinct from that of the adult, and metamorphosis
marks the transition from one pattern to the other. Climax of metamorphosis is
characterized by significant elevations in thyroid hormones, glucocorticoid hormones, and the
pituitary hormones, prolactin and growth hormone. Previously, we and others have shown that
elevated levels of unbound glucocorticoid hormones found at climax of metamorphosis are associated
with a natural decline in lymphocyte numbers, lymphocyte viability, and mitogen-induced
proliferation. Here we present evidence that the mechanism for loss of lymphocytes at
metamorphosis is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function and
loss of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo treatment
with the glucocorticoid receptor antagonist, RU486, whereas the mineralocorticoid receptor
antagonist, RU26752, is poorly effective. These observations support the hypothesis that loss
of larval lymphocytes and changes in lymphocyte function are due to elevated concentrations
of glucocorticoids that remove unnecessary lymphocytes to allow for development of immunological
tolerance to the new adult-specific antigens that appear as a result of metamorphosis
Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis
Metamorphosis in amphibians presents a unique problem for the developing immune
system. Because tadpoles are free-living, they need an immune system to protect against
potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific
molecules to which the tadpole immune system must become tolerant. We
hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself
responses by largely discarding the larval immune system at metamorphosis and
acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we
examined the influx and expansion of host T-cell precursors in the donor thymus of
normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor
thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of
metamorphosis does not prevent this exchange of cells. The implanted thymuses export
T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in
normally developing frogs but is retained to a greater extent if metamorphosis is
inhibited. These studies confirm previous observations of a metamorphosis-associated
wave of expansion of T cells and demonstrate that it is not dependent on the relatively
high concentrations of thyroid hormones required for metamorphosis. Although some
larval T cells persist through metamorphosis, others may be destroyed or the larval
population is significantly diluted by the expanding adult population
Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus
The major histocompatibility complex (MHC) is a cluster of genes encoding products central
to all major functions of the vertebrate immune system. Evidence for an MHC can be found
in all vertebrate groups that have been examined except the jawless fishes. Expression of
MHC class I and class II antigens early in ontogeny is critically important for development
of T lymphocytes capable of discriminating self from nonself. Because of this essential role
in T-cell development, the ontogeny of MHC expression in the South African clawed frog,
Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis.
We therefore examined the possible role of thyroid hormones (TH) in the induction
of class I. By flow cytometry, a small amount of class I expression was detectable on
splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the
amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis
is associated with increased intensity of class I expression. Neither inhibition nor acceleration
of metamorphosis altered the timing of onset of class I expression. However, inhibition
of metamorphosis prevented the increase in class I expression characteristic of adult
cell populations. Because expression was not accelerated in TH-treated frogs or delayed in
metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that
induce expression, although they seem to be required for the upregulation of class I expression
occurring at metamorphosis. Differences in the pattern of expression in different subpopulations
of cells suggest a complex pattern of regulation of expression of class I antigens
during ontogeny
Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus
The major histocompatibility complex (MHC) is a cluster of genes encoding products central
to all major functions of the vertebrate immune system. Evidence for an MHC can be found
in all vertebrate groups that have been examined except the jawless fishes. Expression of
MHC class I and class II antigens early in ontogeny is critically important for development
of T lymphocytes capable of discriminating self from nonself. Because of this essential role
in T-cell development, the ontogeny of MHC expression in the South African clawed frog,
Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis.
We therefore examined the possible role of thyroid hormones (TH) in the induction
of class I. By flow cytometry, a small amount of class I expression was detectable on
splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the
amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis
is associated with increased intensity of class I expression. Neither inhibition nor acceleration
of metamorphosis altered the timing of onset of class I expression. However, inhibition
of metamorphosis prevented the increase in class I expression characteristic of adult
cell populations. Because expression was not accelerated in TH-treated frogs or delayed in
metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that
induce expression, although they seem to be required for the upregulation of class I expression
occurring at metamorphosis. Differences in the pattern of expression in different subpopulations
of cells suggest a complex pattern of regulation of expression of class I antigens
during ontogeny