Findings have potential impact on vaccine design
Antibodies protect us from infection by binding themselves to pathogens and labeling them for destruction by killer white blood cells. These can be generated naturally during infection or induced by vaccination.
Antibodies are produced by immune cells called B lymphocytes that depend on “help” from other white blood cells called CD4+ helper T cells. It was previously established that a subset of CD4+ T cells, named T follicular helper cells, or Tfh cells, are specifically geared towards helping B cells. However, the signals needed to generate these Tfh cells are not completely known.
A recent study conducted by researchers at McGill University in Montreal and at the Garvan Institute of Medical Research in Sydney, Australia, and published in the journal Immunity is the first to identify integrins – a family of cell surface adhesion molecules – as critical for generating and maintaining the Tfh cell population. “While integrins were known to promote the migration and activation of T cells, these molecules have never before been identified as playing a role in Tfh cell development and protective antibody responses,” explains Dr. Irah King, Assistant Professor, Department of Microbiology and Immunology at McGill and the study’s senior author.
The researchers are focused on understanding how immune cells communicate with their local environment to promote protective immune responses relevant to human disease. They are particularly interested in immunity at barrier sites such as the gut, skin and lung as these tissues face the complex task of maintaining homeostasis while directly interacting with the outside world.
“After studying how immune cells migrate through our tissues, we came to discover that making antibodies required some of the same pathways that protect us from infection,” says Dr. King. “Furthermore, when we blocked or genetically deleted integrin function in mice, they exhibited compromised antibody responses and were not protected from intestinal helminth (worm) infection, a type of pathogen that infects over 2 billion people worldwide.”
A lack of Tfh cells leads to an inability to produce protective antibody responses resulting in susceptibility to infection and ineffective vaccination strategies. Conversely, uncontrolled Tfh cell responses can lead to the development of antibodies that attack our body’s own tissues resulting in autoimmune disease such as Lupus. “Understanding the mechanisms by which these cells are regulated can contribute to both promoting health and preventing disease,” notes Alex Meli, a PhD student in Dr. King’s laboratory and first author of the publication. “As pharmaceutical agents that modulate integrin function already exist, these proteins may prove to be an exciting and novel target for controlling Tfh responses that can affect millions of people by influencing vaccine design and the treatment of autoimmune disorders.”
This study was supported with funding from the Canadian Institutes of Health Research.
“The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance.” Meli, et al.
November 23, 2016