Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytotoxic T lymphocyte (CTL) response was the strongest at the site of infection—the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system.