The downside to lymphocytes

Abstract

Lymphocytes are required to fight off invading microbes—T cells to seek out and kill infected cells, and B cells to produce pathogen-specific antibodies. But a study by Carrero and colleagues (page 933) suggests that, in some situations, having lymphocytes is not such a good thing. Figure 1 Dying lymphocytes (red) inhibit the early clearance of L. monocytogenes (green) from the spleen. Two decades ago, this group showed that lymphocyte-deficient mice are up to 1,000 times better than normal mice at controlling bacterial growth during the first few days of infection with Listeria monocytogenes. They speculated that mice born without lymphocytes might have developed a more efficient innate immune response—much like people who are born blind develop a heightened sense of smell and more acute hearing. This idea made sense because innate immune cells—such as macrophages and neutrophils—are responsible for killing the bacteria during the initial phase of infection. But the speculation was incorrect. Macrophages from lymphocyte-deficient mice, they now show, are no more adept at killing the bug than those from normal mice. Nor do the deficient mice produce more inflammatory cytokines in response to infection. Instead, the explanation lay in another past observation: that infection with L. monocytogenes causes a massive death of lymphocytes. This bug-induced cell death—which may allow the bacteria to establish an initial foothold in the host—was indeed to blame for the decreased clearance of the bug. When bone marrow-derived lymphocytes were transferred into deficient mice before infection, the transferred cells died and the mice were robbed of their heightened bug-killing ability. The link between cell death and impaired bacterial control was traced to the antiinflammatory cytokine interleukin (IL)-10, which was produced in response to lymphocyte death. In mice lacking IL-10, infection still triggered lymphocyte death but early control of the bug was no longer inhibited. The IL-10 link is not surprising, as macrophage ingestion of apoptotic cells—which accumulate during all immune responses—is known to trigger the production of antiinflammatory cytokines, helping to resolve ongoing immune responses. Although this study shows a downside to lymphocytes, it does not suggest that we would be better off without them. Indeed, although lymphocyte-deficient mice fare better in the short-term, without adaptive immunity the mice fail to clear the infection and the bacteria persist for life.