A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development

Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials.

We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.

HIV prevalence is increasing worldwide because people on antiretroviral therapy are living longer, although new infections decreased from 3.3 million in 2002, to 2.3 million in 2012. Global AIDS-related deaths peaked at 2.3 million in 2005, and decreased to 1.6 million by 2012. An estimated 9.7 million people in low-income and middle-income countries had started antiretroviral therapy by 2012. New insights into the mechanisms of latent infection and the importance of reservoirs of infection might eventually lead to a cure. The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition. Breakthroughs in the prevention of HIV important to public health include male medical circumcision, antiretrovirals to prevent mother-to-child transmission, antiretroviral therapy in people with HIV to prevent transmission, and antiretrovirals for pre-exposure prophylaxis. Research into other prevention interventions, notably vaccines and vaginal microbicides, is in progress. Copyright © 2014 Elsevier Ltd. All rights reserved.