CD4(+) cytotoxic T-lymphocyte activity against macrophages pulsed with bovine herpesvirus 1 polypeptides

Area of Science:

• Veterinary Immunology
• Virology
• Cellular Immunology

Background:

• Bovine herpesvirus 1 (BHV-1) is known to cause immune suppression in cattle.
• The precise mechanisms underlying BHV-1-induced immune suppression remain incompletely understood.
• Understanding these mechanisms is crucial for developing effective control strategies.

Purpose of the Study:

• To investigate the induction and activity of BHV-1-specific cytolytic CD4(+) T lymphocytes (CTL).
• To elucidate the cytotoxic pathways employed by these CD4(+) CTLs against BHV-1 infected cells.
• To explore the potential role of CD4(+) CTLs in the selective removal of antigen-presenting cells during BHV-1 infection.

Main Methods:

• Stimulation of peripheral blood mononuclear cells (PBMC) from BHV-1 immunized cattle.
• Assays to identify and characterize cytolytic effector cells, primarily CD4(+) T lymphocytes.
• Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay to detect apoptosis.
• Use of EGTA, a perforin pathway inhibitor, to differentiate cytotoxic mechanisms.

Main Results:

• Cytolytic effector cells were identified as CD4(+) T lymphocytes.
• These CD4(+) CTLs lysed autologous macrophages infected with BHV-1 or pulsed with BHV-1 polypeptides.
• Apoptosis of target cells was observed, and the cytotoxic activity was mediated by a Fas-dependent pathway, not perforin.
• EGTA inhibited NK cell cytotoxicity but not CD4(+) CTL activity.

Conclusions:

• BHV-1-specific CD4(+) CTLs lyse BHV-1-infected macrophages through a Fas-mediated apoptotic pathway.
• This mechanism suggests a role for CD4(+) CTLs in the selective elimination of viral antigen-presenting cells.
• The findings provide insights into the cellular immune response to BHV-1 and its contribution to immune suppression.