Renewal of Peripheral CD8+ Memory T Cells During Secondary Viral Infection of Antibody-Sufficient Mice

Abstract

Kinetic studies and short pulses of injected 5-bromo-2-deoxyuridine have been used to analyze the development and renewal of peripheral CD8+ memory T cells in the lungs during primary and secondary respiratory virus infections. We show that developing peripheral CD8+ memory T cells proliferate during acute viral infection with kinetics that are indistinguishable from those of lymphoid CD8+ memory T cells. Secondary exposure to the same virus induces a new round of T cell proliferation and extensive renewal of the peripheral and lymphoid CD8+ memory T cell pools in both B cell-deficient mice and mice with immune Abs. In mice with virus-specific Abs, CD8+ T cell proliferation takes place with minimal inflammation or effector cell recruitment to the lungs. The delayed arrival of CD8+ memory T cells to the lungs of these animals suggests that developing memory cells do not require the same inflammatory signals as effector cells to reach the lung airways. These studies provide important new insight into mechanisms that control the maintenance and renewal of peripheral memory T cell populations during natural infections.