Passive transfer of methacholine sensitivity from man to monkey.

A model of human allergic disease, in which nonhuman primates were infused with serum from allergic humans and challenged with appropriate antigen, was used to determine whether the animals also develop hyperreactive airways characteristic of asthma. Anesthetized monkeys were insufflated with increasing concentrations of methacholine aerosol, and changes in pulmonary function were measured. Airway reactivity as assessed by the dose of methacholine aerosol culminating in apnea was determined after infusion of serum from allergic or nonallergic humans or with heated allergic serum. A comparison of the results indicated that only infusion of unheated serum from allergic humans resulted in an increase in airway reactivity to aerosolized methacholine. These results suggest that a factor in the serum of allergic humans may play a role in the hyperreactivity of airways characteristic of asthma.

Experimental immunogenic granuloma of the orbit: transfer of granulomatous hypersensitivity with a subset of T lymphocytes.

An experimental model to investigate orbital granuloma formation in inbred rats was established. Animals sensitized to trinitrophenyl ovalbumin (TNP-OA) and challenged retro-orbitally with TNP-OA covalently linked o Sepharose 4B beads specifically developed a granulomatous response. This granulomatous reactivity was passively transferred into normal animals by lymph node cells, but not by serum antibody from sensitized donors. Lymphocytes which transfer granuloma formation in normal recipients were characterized by cell fractionation and membrane marker analysis. These experiments show that the effector cells capable of transferring granulomatous hypersensitivity are enriched in the lower density fractions on discontinuous Percoll gradients. These cells are lymphoblasts and express the W3/25 helper T lymphocyte marker. It was also demonstrated that lymphoid cells from sensitized donors in the higher density Percoll fraction appear to be incapable of adoptively transferring granulomatous responsiveness directly to normal recipients. However, incubation of these high density lymphocytes with specific antigen resulted in marked enhancement of their ability to transfer the disease. Antigen-induced activation also resulted in an increase in both lymphoblasts and the W3/25 marker. The authors conclude, therefore, that a subset of T cells which are lymphoblasts and express the helper-cell marker is responsible for granuloma formation in sensitized animals and is capable of transferring orbital granuloma formation to non-sensitized normal recipients.