The effector mechanisms used by CD4(+) T cells to control mycobacteria differ between humans and rodent models of TB and should be investigated in additional animal models. In these studies, the bovine model was used to characterize the mycobactericidal CD4(+) T cell response induced by vaccination with the attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG). Antigenic stimulation of peripheral blood CD4(+) T cells from BCG-vaccinated cattle enhanced expression of perforin and IFN gamma in cells expressing a CD45RA(-)CD45RO(+)CD62L(+) cell surface phenotype, enhanced transcription of granulysin, IFN gamma, perforin, IL-4, IL-13, and IL-21, and enhanced anti-mycobacterial activity of CD4(+) T cells against BCG-infected macrophages. (c) 2007 Elsevier Ltd. All rights reserved.