Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells

CD154 is necessary for mice to clear a Cryptosporidium parvum infection, bu t 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, wh ile RAG(-/-) controls were unable to clear C. par,um infection. Recovery wa s accompanied by an increase in the number of splenic T cells with the CD44 (high) phenotype that characterizes memory cells. To determine whether a C. parvum-infected environment sufficed to activate transgenic T cells, we re constituted C. parvum-infected BALB/c SCID mice with DO11.10 RAG(-/-) splen ocytes, Fecal excretion of C. parvum antigen ceased in the 12 weeks followi ng the adoptive transfer, unless the mice were also injected with tolerizin g doses of ovalbumin. DO11.10 T cells were found in the submucosa of C. par vum-infected, but not uninfected, BALB/c SCID hosts within 18 h of injectio n, The transferred DO11.10 T cells divided and acquired a CD44(high) memory phenotype in C. parvum-infected, but not uninfected, recipients. DO11.10 s plenocytes from CD154 knockout donors failed to clear a C. parvum infection , confirming a requirement for CD154 in recovery, In vitro, the DO11.10 cel ls did not proliferate in response to C. parvum antigen, and a tBlast GenBa nk search revealed no matches between the ovalbumin peptide and C. parvum D NA sequences. C. parvum-infected SCID mice given RAG(-/-) CD8+ T cells with a Listeria-specific transgene did not recover from C. parvum infection. Ou r 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.