Host Defense in Cryptococcosis. III. Protection of Nude Mice by Thymus Transplantation

Abstract

Congenitally athymic (nude) BALB/c mice, which are homozygous for the nu gene, are extremely susceptible to challenge with Cryptococcus neoformans. Groups of nude mice received transplants of thymus tissue obtained from either heterozygous (nu/+) mice or normal BALB/c mice not carrying the nu gene. Survival and delayed-type hypersensitivity were measured after challenge with cryptococci. Mice that received thymus tissue from a heterozygous (nu/+) or normal BALB/c mouse donor had markedly prolonged survival after challenge. In addition, mice that received thymus tissue from normal BALB/c mice developed delayed-type hypersensitivity to cryptococcal antigens following challenge. These studies indicate that transplantation of thymus tissue effectively increases host immune resistance against C. neoformans.

The immune response to fungal infections

“…Infections have also been reported in patients with non‐HIV associated CD4 + T cell lymphopenia (Duncan et al , 1993). Mice with congenital or acquired T cell deficiency have impaired anti‐cryptococcal responses (Graybill & Mitchell, 1979; Graybill et al , 1979). Protective immunity is associated with the Th1 responses.…”

The Cryptococcus neoformans Gene DHA1 Encodes an Antigen That Elicits a Delayed-Type Hypersensitivity Reaction in Immune Mice

“…This predilection for immunosuppressed patients suggests that normal people may resist infection with C. neoformans by competent immune responses to antigenic stimulation. There is considerable experimental support for this concept from the murine model of cryptococcosis (3,6). For example, vaccination with a C. neoformans culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) induces protection against a subsequent cryptococcal infection as well as dermal delayed-type hypersensitivity (DTH) response(s) to cryptococcal antigen (17).…”

The Cryptococcus neoformans GeneDHA1 Encodes an Antigen That Elicits a Delayed-Type Hypersensitivity Reaction in Immune Mice

“…This predilection for immunosuppressed patients suggests that normal people may resist infection with C. neoformans by competent immune responses to antigenic stimulation. There is considerable experimental support for this concept from the murine model of cryptococcosis (3,6). For example, vaccination with a C. neoformans culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) induces protection against a subsequent cryptococcal infection as well as dermal delayed-type hypersensitivity (DTH) response(s) to cryptococcal antigen (17).…”