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Biomedical subjects

M L Tyan

Publications and source records attributed to M L Tyan.

9 recordsLinked to original sources

Development of immune competence.

Present evidence indicates that the precursors of B- and T-cells can be found in the extra-embryonic tissues four days after implantation (day 5) and that by the following day (day 10) certain of the B-cell precursors have differentiated to the stage of the antigen-binding cell. Cells able to secrete antibody are not detected, however, until the later stages of pregnancy. B-cell differentiation has been shown to advance in a stepwise manner through several compartments, and the early stages of maturation are independent of thymic or T-cell regulation. The thymic rudiment appears by the 12th day of pregnancy and the reticuloepithelial tissue is quickly colonized by T-stem cells which migrate from the fetal liver. Within 4 days these cells respond to PHA, recognize and respond to allogeneic antigens, and begin to seed to the peripheral lymphoid tissues. During the latter stages of pregnancy and until about the sixth week after birth T-cell mediated suppressor activity predominates. T-cell killer function can be detected in the neonatal thymus shortly after birth, but this activity increases slowly in the peripheral lymphoid tissues. T-cell helper activity increases slowly after birth as suppressor activity declines. The adult levels of helper-suppressor function are approached about six to eight weeks after birth.

Aging

Age-related decrease in mouse T cell progenitors.

Mice were given a lethal dose of whole-body gamma-radiation and injected with a 10(5) or 10(6) marrow cells from 10- to 143-week-old syngeneic donors. Nine days later, colony-forming units (CFU) were counted in the spleens of mice given 10(5) cells, and 15 to 21 days after irradiation thymus weights and in some experiments 3H-thymidine uptake or total thymic cellularity were determined in the recipients of 10(6) cells. It was found that in the majority of mouse strains studied there were no significant changes with age in marrow CFU. In contrast, thymic regeneration was significantly impaired when the recipients received marrow cells from donors 100 weeks of age or older. These observations and results obtained in dose-response and time-course studies are best explained by an age-related decrease in marrow T cell progenitors; however, certain findings suggest that in addition the proliferative capacity of these stem cells may at times be moderately impaired.

Aging

Immunosuppressive properties of mouse amniotic fluid.

Previous reports have suggested that the alpha-fetoprotein present in mouse amniotic fluid is a potent nontoxic immunosuppressant. In the present studies mouse amniotic fluid (1:50) from 9- to 20-day gestations markedly inhibited the in vitro responses of mouse spleen cells to SRBC, and spleen cells from nonpregnant females were more affected than were cells from pregnant mice. On the other hand, MAF was less effective in depressing antigen- and mitogen-induced proliferation of human blood cells than were NMS or human serum. Human AF and cord sera did not significantly depress the immune responses of cells from mouse or man when added to cultures at concentrations sufficient to achieve levels of alpha-fetoprotein reported to be immunosuppressive if mouse AFP is used. While these studies do not identify the inhibitory agent(s) present in MAF, they do suggest that mouse AFP either is pharmacologically different from human AFP and/or that the immunosuppressive activity attributed to mouse AFP is actually produced by another agent physically associated with it.

Amniotic Fluid

Impaired thymic regeneration in lethally irradiated mice given bone marrow from aged donors.

Mice were given a lethal dose of whole-body gamma radiation and injected with 10(5) or 10(6) marrow cells from 10- to 143-week-old syngeneic donors. Nine days later, colony-forming units (CFU) were counted in the spleens of mice given 10(5) cells, and 21 days after irradiation, spleen and thymus weights were determined in the recipients of 10(6) cells. It was found that there were no significant changes with age in marrow CFU or in the ability of marrow cells to repopulate host spleens. In contrast, thymic regeneration was significantly impaired when the recipients received marrow cells from donors 117 weeks of age or older. These observations suggest that with aging there is a decrease in marrow T-cell progenitors and/or a decline in their proliferative capacity.

Aging

Allogeneic radiation chimeras. Long-term studies.

Lethally irradiated mice protected with allogeneic fetal liver cells or with syngeneic or allogeneic marrow and spleen cells treated with antisera to mouse immunoglobulins or to the T cell-associated theta antigen and their controls were observed for up to 750 days. The best survival rates were found in the large groups given syngeneic marrow and spleen or allogeneic fetal liver cells (70-85% 700-day survival); in contrast, 43% of the group injected with allogeneic cells treated with anti-theta serum and 19% of those given antiimmunoglobulin-treated cells were alive 700 days postradiation. Pulmonary infection was the most frequent cause of death of long-term survivors in all groups. Tumor incidence was increased in recipients of allogeneic cells (13% versus 4% among syngeneic chimeras), but the renal pathology seen in these groups was no greater than that noted in the syngeneic controls. Beginning 600 days after irradiation, mice from experimental and control groups were killed and their spleens were cultured with thymus-dependent antigens and the mitogens concanavalin A and lipopolysaccharide, Escherichia coli. The most frequent finding in all groups was mild to moderate impairment of T cell-dependent responses.

Animals

Steric hindrance of CON A receptor sites by antigen: a possible explanation of Ir regulated responses.

Spleen cells from mice that respond poorly (C57BL/6) or well (CBA, C3H/HeJ AND B6D2F1) to DNP-BGG, an antigen under Ir gene regulation, were cultured with the T cell mitogen Con A and varying concentrations of DNP-BGG and DNP-KLH. It was found that DNP-BGG dpressed the responses of C57BL/6 spleen cells to Con A stimulation to a much greater degree than did DNP-KLH; the Con A stimulated responses of spleen cells from the other strains were impaired equally and less severely by both antigens. The possible implications of these findings with regard to Ir gene regulation of thymus-dependent immune responses were discussed.

Animals