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

Summary 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 epilope of the intestinal trophozoites (characterized by the binding capacity of monoclonal antibody MoAbG 10/4) as well as cellular and humoral immune parameters of the hosts were followed during the course of infection. Self‐cure was observed in hetcrozygous (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. Trophozoiles 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 (>99%) until termination of the experiment (day 25 p.i.); therefore, antigenie 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 excystmenl followed by infection in a new host.