Regulation of the Primary Immune Response to Ovalbumin in Mice: Activation of T Cells Mediating Delayed-Type Hypersensitivity, Nonspecific Help, and Specific Help, and Their Sensitivity to Radiation

Abstract

We have previously shown that the immune response to ovalbumin (OVA) in mice is controlled by at least four genes. The purpose of the studies reported here was to investigate the site of action of the genes regulating the response to OVA. To this end, helper T cell functions were studied in responder (BDF₁) and nonresponder (A/J) mice by using three approaches.

In the first approach, the antibody response to limiting and nonlimiting doses of TNP-OVA was studied. When mice were immunized with limiting doses of TNP-OVA, anti-TNP antibodies were elicited but anti-OVA antibodies were not. These findings suggest that OVA-specific helper T cells are not the limiting factor in the anti-OVA antibody responses.

Helper T cell functions were also measured in in vitro assays. Two kinds of helper T cell activity were measured. “Nonspecific” helper T cell activity (the bystander effect) was determined by measuring the ability of OVA-primed spleen cells to help the anti-sheep red blood cells (SRBC) antibody response in cultures stimulated with SRBC and TNP-OVA. Antigen-specific helper activity was determined by measuring the ability of OVA-primed spleen cells to help the anti-TNP antibody response in cultures stimulated with TNP-OVA. The results indicate that in vivo-priming doses of OVA that do not elicit a delayed-type hypersensitivity (DTH) response or a primary antibody response prime for both “nonspecific” and antigen-specific helper T cells. These findings suggest that the genes regulating the immune response to OVA do not control activation of helper T cells.

These T cell subpopulations that recognize OVA can be further distinguished by virtue of their sensitivity to radiation. The DTH effector cells and cells responsible for “nonspecific” help are not sensitive to 1000R. In contrast, the specific helper activity is sensitive to 1000R. The subsets that are not sensitive to radiation are distinguished by their independent activation by OVA.