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Infection and Immunity, May 2000, p. 2663-2670, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Eradication of Cryptosporidium parvum Infection by Mice with Ovalbumin-Specific T Cells

Kara Lukin, Mary Cosyns, Tom Mitchell, Milton Saffry, and Anthony Hayward*

Departments of Immunology and Pediatrics and the Barbara Davis Childhood Diabetes Center, University of Colorado School of Medicine, Denver, Colorado 80262

Received 14 February 2000/Accepted 16 February 2000

CD154 is necessary for mice to clear a Cryptosporidium parvum infection, but whether this ligand has to be expressed on T cells with specificity for C. parvum has not been determined. We infected DO11.10 (ovalbumin specific) T-cell receptor transgenic mice that had been bred to a RAG-/- background with C. parvum and found that the infection was cleared within 6 weeks, while RAG-/- controls were unable to clear C. parvum infection. Recovery was accompanied by an increase in the number of splenic T cells with the CD44high phenotype that characterizes memory cells. To determine whether a C. parvum-infected environment sufficed to activate transgenic T cells, we reconstituted C. parvum-infected BALB/c SCID mice with DO11.10 RAG-/- splenocytes. Fecal excretion of C. parvum antigen ceased in the 12 weeks following the adoptive transfer, unless the mice were also injected with tolerizing doses of ovalbumin. DO11.10 T cells were found in the submucosa of C. parvum-infected, but not uninfected, BALB/c SCID hosts within 48 h of injection. The transferred DO11.10 T cells divided and acquired a CD44high memory phenotype in C. parvum-infected, but not uninfected, recipients. DO11.10 splenocytes from CD154 knockout donors failed to clear a C. parvum infection, confirming a requirement for CD154 in recovery. In vitro, the DO11.10 cells did not proliferate in response to C. parvum antigen, and a tBlast GenBank search revealed no matches between the ovalbumin peptide and C. parvum DNA sequences. C. parvum-infected SCID mice given RAG-/- CD8+ T cells with a Listeria-specific transgene did not recover from C. parvum infection. Our data suggest that antigen-nonspecific CD4+ T-cell effector mechanisms in combination with the innate arm of the immune system are sufficient for the eradication of C. parvum infection.

* Corresponding author. Mailing address: B140, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. Phone: (303) 315-7462. Fax: (303) 315-4892. E-mail: anthony.hayward{at}uchsc.edu.

Infection and Immunity, May 2000, p. 2663-2670, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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