John W. Jutila

Reconstitution of the in vitro immune response of congenitally thymusless (nude) mice.

Summary Spleen cell cultures from congenitally thymusless (nude) mice were found to be unresponsive to SE in vitro. The addition of 5.0 × 107 thymus cells from Balb/c or littermate animals to “nude” spleen cell cultures enabled these cultures to respond to SE. An in vitro response to SE could also be obtained by addition of normal spleen cells from Balb/c mice. As few as 2.4 × 105 Balb/c spleen cells established an immune response in nude spleen cell cultures. The reconstitution of nude spleen cell cultures with thymus cells indicates that while a deficiency of thymus-derived cells exists in nude mice, they have functional bone marrow-derived cells. We thank R. W. Dutton for instructing one of us (D.P.A.) in the use of the Mishell-Dutton Procedure, and R. C. Roberts and D. S. Falconer for providing the breeding nucleus of mice carrying nude.

Immune Response of Congenitally Thymusless Mice to Heterologous Erythrocytes

Summary Hemagglutinin and hemolysin production by congenitally thymusless (“nude”) mice in response to intraperitoneal injection of 107, 108, 109, or 1010 sheep erythrocytes (SE) was significantly lower than in normal littermate controls. The plaque-forming cell response of nudes was also impaired. Rosette-forming cells (RFC) were observed in unimmunized nude mice. Injection of SE did not result in the formation of increased numbers of RFC in nude mice, whereas littermate controls responded strongly. The authors express appreciation to R. C. Roberts and D. S. Falconer for providing the breeding nucleus of mice carrying nude and to Mrs. Billie Welty for excellent technical assistance.

Immunosuppression of congenitally athymic (nude) mice with heterologous anti-immunoglobulin heavy-chain antisera

Abstract Congenitally athymic (nude) mice have been shown to be far more sensitive than their phenotypically normal littermates to immunosuppression by anti-Ig antisera. Anti-μ suppression of nude mice was seen to result in complete and stable loss of IgM and IgA as well as severe reductions in IgG1 and IgG2 levels. Anti-α treatment of nudes resulted only in complete and stable loss of IgA; similarly, anti-γ1γ2 treatment achieved only class-specific reductions of IgG1 and IgG2 levels, but these reductions recovered slightly during suppression. Nude mice were more severely immunosuppressed than their phenotypically normal littermates upon anti-Ig treatment and demonstrated much less ability to recover from such suppressive effects. The significance of these observations regarding thymus dependency of immunoglobulin synthesis in nude mice is discussed.

Congenitally Athymic (Nude) Mice and Their Application to the Study of Immunity and Aging

Numerous studies in several mammalian species, including man, mice, rats, and hamsters have established a strong relationship between the aging process and a decline in the functional capacity of the immune system (Walford, 1969). The socalled immunologic theory of aging predicts that genetic and induced defects in the immune apparatus may seriously compromise the general health of man or animals by failing to thwart infections and neoplasia on the one hand, and, on the other, by responding to self-antigens to produce destructive autoimmune disorders.