Biomedical subjects

P McCullagh

Publications and source records attributed to P McCullagh.

90 records · Page 5Linked to original sources

PubMed1976

Radiosensitivity of suppressor cells in newborn rats.

The resistance of neonatal rats to sustaining adoptive immune responses against heterologous erythrocytes following the transfter of normal thoracic dust lymphocytes was examined. Irradiation of the neonatal rat at levels as low as 350 rad was found to be effective in overcoming this resistance, although preliminary exposure to antigen could interfere with facilitation of adoptive responses by irradiation. It is suggested that the failure of the neonate to sustain adoptive immune responses is explicable on the basis of an active suppression and, as a corollary, unresponsiveness resulting either from macrophage immaturity or the transfer of maternal antibody is discountered as a likely explanation for the immunological behavior of the newborn rat towards the antigens examined.

Animals↗

PubMed1976

Role of the thymus in suppression of immune responses in newborn rats.

The role of thymus-derived cells in controlling the process of immunological maturation in the neonatal rat has been examined. Thymectomy performed on the day of birth resembled irradiation given at this time in that it permitted adoptive immune responses to sheep erythrocytes to be initiated in the neonatal host. Whereas the consequences of irradiation could be demonstrated if antigenic challenge was given of the following day, adoptive responses were not sustained unless an interval in excess of 24 h had elapsed after thymectomy, suggesting that extra-thymic suppressor cells persist for at least this period. Suppression of adoptive responses was achieved in irradiated hosts with thymus cells obtained from rats on their day of birth but not with cells from older donors. Using the transfer of allogeneic lymphocytes as a stimulus, antibody-forming cell precursors were shown to be plentiful in the newborn rat and it was accordingly suggested that thymic suppressor cells are reponsible for the poor responsiveness of newborn rats to antigenic challenge.

Animals↗

PubMed1976

Facilitation of the growth of an allogeneic tumour by suppressor cells in newborn rats.

The intravenous injection of as few as 15 Walker tumour cells into newborn rats consistently resulted in the development of pulmonary metastases and the death of the recipient within 2 weeks. Neither the outcome of tumour cell injection nor the interval until death could be modified by transferring 2 x 10(7) lymphocytes from tumour-immune adult rats to the neonataal hosts. In contrast with this failure to transfer adoptive anti-tumour immune responses to intact recipients, the administration of 350 rad irradiation before transfer of 10(6) immune lymphocytes constantly afforded protection against inoculated tumour cells. The simultaneous transfer of neonatal thymus cells with immune lymphocytes interfered with the establishment of an adoptive response in the irradiated newborn. Intiation of a graft-versus-host response in F1 hybrid neonates by injecting parental strain lymphocytes conferred resistance to tumour growth of the recpient, the magnitude of this effect increasing with the strength of the graft-versus-host reaction.

Animals↗

PubMed1976

Suppressor cells in homograft tolerant rats.

If sufficient normal syngeneic lymphocytes to effect skin graft rejection are transferred to homograft tolerant rats, a prolonged period elapses before lymphoid cells from the recipient acquire normal levels of GvH responsiveness against tissues of which the donor was previously tolerant (Silvers and Billingham, 1970; Elkins, 1972; Miyamoto and McCullagh, 1974). Although the ability of lymphoid populations of such animals to mount GvH reactions can be demonstrated to reside in donor type cells during the weeks immediately after transfer, reactive cells are ultimately derived from the host itself (Elkins, 1973; Miyamoto and McCullagh, 1974). Not only are lymphoid cells from tolerant rats which have been injected recently with normal lymphocytes poorly responsive in a GvH assay, but they have been observed in some experiments to suppress the GvH activity of normal syngeneic lymphoid cells (Elkins, 1972; Atkins and Ford, 1972). It is not clear whether the cells mediating suppression of the normal lymphocytes were derived from the tolerant host itself or, alternatively, from the normal lymphocytes injected into it to terminate the tolerant state. The present experiments sought to delineate the origin of any suppressor cells within populations of lymphocytes collected from rats in which tolerance had recently been terminated. The indicate that suppression of the normal donor cells within such populations may be exerted by cells derived from the tolerant host.

Animals↗

PubMed1976

Modification of the tolerant state by neonatal thymectomy.

Immunological tolerance of sheep erythrocytes was induced by repeated antigenic challenge of rats which had been thymectomized on the day of birth. Thoracic duct lymphocytes from these thymectomized tolerant rats failed to mount adoptive responses against sheep erythrocytes and interfered with the capacity of normal lymphocytes to mount such responses. However, in sharp contrast with non-thymectomized tolerant rats, thymectomized animals responded well to sheep erythrocytes if challenge was accompanied by the injection of normal syngeneic lymphocytes. It is likely that the cells that are lacking from tolerant rats as a consequence of neonatal thymectomy are identical with the radiosensitive cells that suppress normal lymphocytes transferred to intact tolerant rats.

Animals↗

PubMed1975

The mechanism of unresponsiveness in lymphocytes specifically selected by antigen in normal rats.

The immunological potentialities of populations of thoracic duct lymphocytes collected from rats recently challenged with sheep erythrocytes were compared with those of lymphocytes from rats immunologically tolerant of this antigen. Both "selected" and tolerant populations fail to mount immune responses to sheep erythrocytes in irradiated syngeneic hosts but can do so if transferred to semi-allogeneic recipients. If co-cultivated with normal lymphocytes in irradiated hosts, both types of population can modulate the responsiveness of the former to sheep erythrocytes. Supplementation of normal lymphocytes with "selected" populations collected earlier than 28 hours after challenge of the donors tends to result in augmented responses while later collections are more likely to be associated with suppression. Consequently, it is suggested that "selected" populations are unresponsive because of the presence of specifically activated cells rather than as a result of their depletion. The influence of "selected" populations on the responsiveness of normal lymphocytes is attributed to this content of activated cells.

Animals↗

PubMed1974