Cryptosporidium infection in an adult mouse model: Independent roles for IFN-γ and CD4+ T lymphocytes in protective immunity

Beth L.P. Ungar*, Tzu Cheg Kao, Jennifer A. Burris, Fred D. Finkelman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


Cryptosporidium is a protozoan parasite that can cause chronic life-threatening diarrhea in immunocompromised persons. Host immune responses are poorly understood, an impediment to development of effective therapy. In mice, normal adult BALB/c animals resist infection whereas chronic symptomatic cryptosporidiosis develops in adult nude mice and in neonatally infected BALB/c mice treated with anti-CD4 mAb. To define further the immune defects that allow mice to be infected with Cryptosporidium, adult BALB/c mice were treated with cytolytic anti-CD4 or anti-CD8 or with neutralizing anti-IFN-γ or anti-IL-2 mAb. Chronic infection, manifested by continuous shedding of sparse but statistically significant numbers of oocysts, occurred with antiCD4 ± anti-CD8 mAb treatment although anti-CD8 mAb treatment alone did not allow infection. Treatment with anti-IFN-γ mAb greatly enhanced oocyst shedding but infection was self-limited. Treatment with a combination of anti-CD4 and anti-IFN-γ mAb permitted both chronic infection and shedding of large numbers of oocysts. Furthermore mice treated initially with anti-CD4 mAb showed a substantial increase in oocyst shedding when later treated with anti-IFN-γ mAb; and mice treated initially with both mAbs showed a decline in oocyst shedding when anti-IFN-γ mAb was stopped. Anti-IFN-γ mAb treatment of congenitally athymic adult BALB/c mice led to an approximately a 75-fold increase in oocyst shedding. Treatment of adult BALB/c mice with anti-IL-2 mAb did not permit Cryptosporidium infection. These results suggest that redundant immunologic mechanisms limit Cryptosporidium infection such that both CD4+ cells and IFN-γ are required to prevent initiation of infection whereas either alone can limit the extent (IFN-γ) or duration (CD4+ T cells) of infection. They also suggest that production of IFN-γ by a non-T cell contributes to host immunity.

Original languageEnglish
Pages (from-to)1014-1022
Number of pages9
JournalJournal of Immunology
Issue number3
StatePublished - 1 Aug 1991
Externally publishedYes


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