Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis

Journal of Immunology Research, Aug 2018

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.

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Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis

Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis LOUISE A. ROLLINS-SMITH PATRICK J. BLAIR A. TRAY DAVIS 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. Thymus ontogeny; Xenopus laevis; thyroid hormones; metamorphosis INTRODUCTION The immune system and immune response pattern of Xenopus laevis tadpoles are distinct from that of adults (reviewed in Flajnik et al., 1987; Du Pasquier et a1.,1989) . Tadpoles reject slowly or more frequently become tolerant of major histocompatibility complex (MHC)-disparate skin grafts than adults; and they generally do not reject skin grafts differing by minor histoincompatibilities whereas adults do (Chardonnens and Du Pasquier, 1973; DiMarzo and Cohen, 1982a, 1982b; Obara et al., 1983; Cohen et al., 1985; Rollins-Smith et al., 1988) . The tadpole antibody response to given antigen is generally less heterogenous and antibodies have lower affinities than those of adults (Du Pasquier and Haimovich, 1976; Du Pasqu.ier et al., 1979; Hsu and Du Pasquier, 1984) . Classical class I MHC *Corresponding author. antigens are not expressed by tadpole cells until they near metamorphosis (Flajnik et al., 1986; Flajnik and Du Pasquier, 1988) and class II MHC antigens are expressed on different lymphocyte subpopulations in the tadpole and adult (Du Pasquier and Flajnik, 1990; Rollins-Smith and Blair, 1990a) . All of these studies suggest a significant reorganization of the immune system at metamorphosis. Indeed there is evidence for a major loss of lymphocytes from thymus, spleen, and liver at metamorphosis (Du Pasquier and Weiss, 1973; Rollins-Smith et al., 1984; Cohen et al., 1985) that is exacerbated by thyroxine-driven precocious metamorphosis (Rollins-Smith et al., 1988) . As has been shown for birds (Le Douarin and Jotereau, 1975; Jotereau and Le Douarin, 1982) and mammals (Jotereau et al., 1987), thymus ontogeny in amphibians is characterized by a succesion of waves of T-cell precursors moving into the thymus where they expand, differentiate, and leave as mature T cells (Turpen and Smith, 1989) . In X. laevis, the third wave of detectable expansion occurs in association with metamorphosis (Turpen and Smith, 1989) . Little is known about the intrathymic signals that result in attraction of T-cell precursors during receptive periods. We hypothesized that a thyroid hormone-dependent maturational event in the thymus might be responsible for the metamorphosis-associated period of attractiveness. By implanting triploid (3N) thymuses into agematched diploid (2N) larval hosts that were allowed to metamorphose or were prevented from metamorphosing, we were able to test this hypothesis. The studies were designed to answer two questions. Is the influx and expansion of stem cells in the thymus at metamorphosis a thyroid hormone-dependent phenomenon? Do larval donor-derived T lymphocytes that colonize the spleen persist through metamorphosis? We observed that donor thymocytes are replaced by host-derived cells in about 60 days regardless of whether they undergo metamorphosis. Some donor-derived larval T cells persist in the spleen for at least 1 month after metamorphosis, but their numbers are low. Inhibition of metamorphosis results in the persistence of a greater number of these larval T cells. RESULTS Renewal of Thymocytes at Metamorphosis in Normally Developing Hosts To study the influx and expansion of T-cell precursors in normally developing hosts, a 3N thymus was implanted into a number of age- and stage-matched 2N hosts at days 35-37 (s (...truncated)


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Louise A. Rollins-Smith, Patrick J. Blair, A. Tray Davis. Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis, Journal of Immunology Research, 2, DOI: 10.1155/1992/26251