T cell memory in the lung airways

Abstract

The respiratory tract poses a substantial challenge to the immune system due to its large surface area, an extensive vasculature that is in very close proximity to the external environment, and repeated exposure to potentially pathogenic organisms in the air. Yet many lung pathogens are controlled by appropriate immune responses. The underlying mechanisms of the adaptive cellular immune response in protecting the respiratory tract are poorly understood. Recently, it has emerged that memory CD4(+) and CD8(+) T cells are present in the lung airways, and evidence is mounting that these cells play a key role in pulmonary immunity to pathogen challenge by immediately engaging the pathogen at the site of infection when pathogen loads are low. For example, in the case of respiratory virus infections, there is evidence that both CD4(+) and CD8(+) memory cells in the lung airways mediate substantial control of a secondary respiratory virus infection in the lungs. Here we address recent developments in our understanding of lung airway memory T cells and their role in infectious disease.

Figure 1.

Memory T cells in the lung airways are CD11a^lo. Mice were infected with Sendai virus and lymphocytes isolated from the lung airways and spleen on Day 40 after infection for flow cytometric analysis. Data in the left panels identify CD8⁺ T cells specific for the dominant NP_324-332/K^b epitope of Sendai virus. Data in the right panels are gated on NP_324-332/K^b-specific T cells and show the distinct patterns of CD11a expression on these cells depending on whether they are isolated from the spleen or lung airways.

Figure 2.

T-cell response in the lung airways occurs in distinct phases. T cells responding to a primary respiratory virus infection begin to accumulate in the lung airways around Day 6 after infection and peak numbers are typically present on Day 10 after infection. T cells responding to a secondary respiratory virus infection are comprised of three distinct phases. The first phase involves memory T cells that are already in the lung airways. These cells respond immediately to the infection and their numbers decline rapidly. The second phase involves memory T cells that are rapidly recruited into the lung airways at early stages of the infection (Days 3–6). These cells are nonproliferating. The third phase involves memory T cells that have proliferated in response to antigen and are then recruited into the airways (peaking at Day 7). Taken together, the secondary response is characterized by a sustained T cell response to the infection. In addition, the accumulation of proliferating cells in the lung airways (phase 3 cells) occurs earlier, and is of greater magnitude, than in the primary response.