Blocking studies carried out with anti-H-2 class II antigen antibodies show that H-2 class II molecules are intimately involved in the recognition of Mlsa determinants by unprimed, specifically responsive T cells. The blocking of the anti-Mlsa response by these antibodies were not due to inhibition of IL-1 production by H-2 class II antigen positive macrophages. A strain analysis indicates that the response to Mlsa is regulated by H-2-linked genes and that this effect is exerted at the level of the stimulator cells; however, the response to Mls epitopes does not appear to be H-2 restricted. Finally, the ability of spleen cells from Mls-incompatible mice to induce a state of Mls-specific, clonal deletion type tolerance by neonatal injection, shows that Mls determinants exist in qualitatively allelic forms and suggests that these determinants are recognized by specific clones of T cells.

Animals↗

PubMedDate not supplied

Migration of yolk sac cells to thymus grafts: requirement of prior sojourn in bone marrow (or liver?).

The migration of CBA/HT6T6 haemopoietic cells (adult bone marrow, embryonic liver or yolk sac) to established thymus grafts, in CBA/H 60-day neonatally thymectomized hosts, shows that all three cell types can migrate and divide within the grafts, albeit yolk sac cells appear later after cell injection. This last observation suggested possible intermediate steps, i.e. a sojourn in bone marrow (or liver in the embryos). When the same experiments were performed in hosts that had been pre-treated with 100 muCi of 89Sr (a bone seeking isotope), it was observed that marrow and embryonic liver cells still could migrate to thymus and subsequently generate a population of competent T lymphocytes, while yolk sac cells were incapable of such migration.

Animals↗

PubMedDate not supplied

WEHI-164 clone 2F: in vitro antitumor effects of tumor necrosis factor and gamma-interferon.

Based on their enhanced susceptibility to tumor necrosis factor (TNF), sublines of the BALB/c fibrosarcoma WEHI-164 are more and more frequently being used to measure levels of TNF in cell-free supernatants. In studies aimed at characterizing the cytostatic and cytolytic effects of TNF and gamma-interferon (IFN-gamma) on a highly TNF-sensitive subline of WEHI-164, we show that: (1) the MTT assay which measures viable cell numbers (i.e. both cytostasis and cytolysis) at appropriate target cell numbers is sensitive to less than 0.1 pg/ml of recombinant murine TNF (rmTNF) without the need to add protein synthesis inhibitors such as actinomycin D; (2) using irradiated cells, the MTT assay is significantly more sensitive and measures cell lysis but not stasis; (3) clone 2F is sensitive to the cytostatic, but not cytolytic effects of recombinant murine IFN-gamma; (4) although lysis of 2F by rmTNF requires more than 5 h, a short exposure (30-60 min) to rmTNF is sufficient to trigger the lytic process, and (5) lysis of 2F is not cell-cycle-dependent. The use of highly sensitive indicator cell lines such as 2F allow for the measurement of low levels of TNF present in culture supernatants and for studies into the mechanism of action of TNF. However, sensitivity to other agents such as IFN supports the need to confirm that the antitumor effects seen are due to TNF via neutralizing antibody.

Animals↗