Antigenic variation in Giardia lamblia: infection of congenitally athymic nude and scid mice.

Athymic nude mice of the outbred Zur:ICR-nu and inbred BALB/c strain and scid mice were infected with a cloned human isolate of Giardia lamblia (GS/M-83-H7). Changes in the expression of the major surface epitope of the intestinal trophozoites (characterized by the binding capacity of monoclonal antibody MoAbG10/4) as well as cellular and humoral immune parameters of the hosts were followed during the course of infection. Self-cure was observed in heterozygous (nu/+) BALB/c mice by day 22 post-infection (p.i.) and in heterozygous (nu/+) Zur:ICR-nu strain by day 65 p.i. Homozygous (nu/nu) mice of both strains remained chronically infected until end of the experiments (day 45 p.i. for BALB/c mice and day 122 p.i. for Zur:ICR-nu mice, respectively). Only heterozygous (nu/+) mice were able to mount a gut-associated (Peyer's patch) lymphoproliferative response to G. lamblia antigen. Therefore, T-cell dependent mechanisms were necessary for a self-cure. Antigenic variation occurred in all nu/+ and nu/nu animals of both strains. Trophozoites expressing the major surface epitope (assessed by direct immunofluorescence with FITC-labelled MoAb G10/4) decreased to zero by day 22 p.i. In contrast, the proportion of trophozoites expressing the major surface epitope in infected scid mice remained at the initial level (greater than 99%) until termination of the experiment (day 25 p.i.); therefore, antigenic variation did not occur. All nu/nu and nu/+ mice but not scid mice demonstrated a humoral immune response to G. lamblia antigen. These experiments suggest functional B-cell dependent mechanisms are most likely responsible for the surface antigen switch. Transfer of infection occurred naturally from experimentally infected scid-mice to their mother, proving the initial antigenic surface variant remains unchanged after encystment and subsequent excystment followed by infection in a new host.