Low numbers of intestinal Shiga toxin-producing E. coli correlate with a poor prognosis in sheep infected with bovine leukemia virus

Healthy ruminants carry intestinal Shiga toxin (Stx)-producing Escherichia coli (STEC). Stx has antiviral activities in vitro and STEC numbers correlate with reduced early viremia in sheep experimentally infected with bovine leukemia virus (BLV). This study assessed the impact of intestinal STEC on BLV-induced disease for one year post-BLV-challenge. High STEC scores (CFU/g feces x frequency of STEC-positive samples) correlated with good health, whereas poor weight gain, distress, and tumor development occurred only among animals with low STEC scores. STEC carriage was associated with increased percentages of B cells in peripheral blood.

Unique features of bovine lymphocytes exposed to a staphylococcal enterotoxin

We previously demonstrated that stimulation of bovine peripheral blood mononuclear cells (PBMCs) with staphylococcal enterotoxin C (SEC), led to an inversion of the CD4(+):CD8(+) T cell ratio and generation of an atypical CD8(+) T cell subpopulation expressing CD26. In the present study, we examined T cell apoptosis and proliferation profiles of PBMC subpopulations in cultures stimulated with SEC. Unlike when stimulated with concanavalin A, nucleic acid synthesis in bovine PBMC cultures stimulated with SEC was low during the first four days but increased greatly on day 5. In contrast, nucleic acid synthesis in human PBMC cultures stimulated with SEC increased continuously. To investigate the mechanism of delayed bovine T cell proliferation, various cell phenotypes were monitored. The inversion of the bovine CD4(+):CD8(+) T cell ratio in PBMC cultures stimulated by SEC was associated with higher proliferation and lower apoptosis of CD8(+) T cells compared to CD4(+) T cells. The mRNA levels for interleukin (IL)-4 and IL-13 were sustained over 4 days but IL-12 mRNA levels dropped to background on day 2. These data suggest that SEC induces a prolonged Th-2- biased microenvironment, and together with the inversion of the bovine CD4(+):CD8(+) T cell ratios in bovine PBMC cultures with SEC, may in part explain the inability of the mammary immune system to establish an effective response to Staphylococcus aureus infections.

Immunosuppression by T regulatory cells in cows infected with Staphylococcal superantigen

Our recent study has provided that the in vitro SEC-induced proliferation of bovine T cells is preceded by a period of a non-proliferative immunoregulation of T cells that may be associated with cytokine production regulated by type 1 or type 2 T cells. Inversion of CD4+:CD8+ T cell ratio and induction of CD8+T cells with immunoregulatory activity could increase the probability of intracellular survival of Staphylococcus aureus (S. aureus). The increase of activated CD8+(ACT2+ BoCD8+) T cells in cows with mastitis caused by S. aureus may be associated with immune-regulatory function in the bovine mammary gland. The difference and similarity between bovine activated CD8+ T cells (CD8+ CD26+)and well-established human CD4+ CD25+ T regulatory (Tr)cells may help to reveal their unique immune regulatory system in the host infected with S. aureus.