Proliferative expansion and acquisition of effector activity by memory CD4⁺ T cells in the lungs following pulmonary virus infection

The memory CD4⁺ T cell response to the respiratory syncytial virus (RSV) attachment (G) protein in the lungs of primed BALB/c mice undergoing challenge pulmonary RSV infection is dominated by effector T cells expressing a single Vβ-chain, Vβ14. We have used Vβ14 expression to examine the kinetics of the activation, accumulation, and acquisition of the effector activity of memory CD4⁺ T cells responding to pulmonary infection. This analysis revealed that proliferative expansion and effector CD4⁺ T cell differentiation preferentially occur in the respiratory tract following rapid activation within and egress from the lymph nodes draining the respiratory tract. These findings suggest that, in response to natural infection at a peripheral mucosal site such as the lungs, memory CD4⁺ T cell expansion and differentiation into activated effector T cells may occur predominantly in the peripheral site of infection rather than exclusively in the lymph nodes draining the site of infection.