Compromised Influenza Virus-Specific CD8 + -T-Cell Memory in CD4 + -T-Cell-Deficient Mice

Abstract

The primary influenza A virus-specific CD8 + -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b +/+ and CD4 + -T-cell-deficient I-A b −/− mice. Comparable levels of virus-specific cytotoxic-T-lymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 + subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b −/− mice. Thus, though the capacity to mediate the CD8 + -T-cell effector function is broadly preserved in the absence of concurrent CD4 + -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.