COPD patients were shown to show a number of changes associated with immunosensitivity, in particular a decrease in CD4 + and CD8 + T cells, which are key elements in the immune system. The study involved 92 individuals divided into four groups: COPD patients (21), smokers with no signs of lung disease (22), healthy elderly subjects (29) and young adults (20).
After analyzing blood samples from all four groups to detect seven markers associated with late differentiation, senescence and attenuation of immune system cells for each of these groups, the researchers concluded that COPD patients had cells that expressed all the markers in question and that this configured for premature aging of the immune system.
It affects about 64 million people worldwide, according to the World Health Organization (WHO), including about 6 million in Brazil, and smokers or former smokers account for 60% of cases.
“As the population ages, it is important to understand the mechanisms involved in immunosensitization for several reasons. Knowing how to treat organisms in older people, with their increased vulnerability to cancer and infections, and weaker responses to vaccines, can help us find better “This study provides additional information on what is happening and on possible interventions,” said Gil Benard, author of the article. Benard is a professor at FM-USP and a researcher at its Dermatology and Immunodeficiency Laboratory. The study was supported by FAPESP.
According to Juliana Ruiz Fernandes, first author of the article, analysis of blood samples from COPD patients in the study showed faster senescence of T cells than in healthy subjects of the same age. “The phenotype of their T cells appeared older than humans without the chronic inflammatory process,” she told Agncia FAPESP. The study was part of her doctoral research at FM-USP.
The group of smokers suggested that moderate to intense smoking did not accelerate immunosensitivity compared with the results for healthy adults. “COPD affected patients more than aging, which drastically weakened the immune system,” said Thalyta Nery Carvalho Pinto, a doctoral student and other author of the article.
In his master’s dissertation from 2016, Fernandes studied the effects of physical exercise on the immune response in COPD patients, which showed that rehabilitation slowed cellular aging on certain parameters and increased the contribution of T cells to the immune response. The results indicated that COPD patients had a higher proportion of exhausted T cells and impaired function. “Our recent study looked at the cell types involved in COPD and aging,” she said.
Immunogenesis is defined as a deterioration in the function of the immune system during aging. It affects both innate and adaptive immunity. It is characterized by a decrease in “naive” T cells, which have matured but have not yet been activated by hitting their antigens, and an increase in “memory” (antigen-perceived) T cells.
Memory T cells undergo three stages of development during a person’s lifetime. In the first, which lasts until about 10 years of age, a pool of naive cells becomes memory cells in response to stimulation of specific antigens. In the second (known as memory homeostasis), circulating memory T cells reach a plateau and remain there until adulthood. In the third, the frequency and functionality of these cells change after a long period of stability, leading to an increased susceptibility to infections caused by immune destruction as part of the person’s aging and physiological decline.
In the study, the researchers found that this stage of immune system development was disrupted in COPD patients, who showed a reduced pool of naive cells available to respond to pathogens, and (paradoxically) a larger proportion of these cells were impaired by late differentiation, senescence or fatigue than healthy older adults and smokers.
“We also found that the immunosensitivity and the changes seen in COPD patients were most pronounced in CD8 + T cells, which can be considered ‘soldiers’ carrying out the immune system’s orders by killing intruders,” Benard said.
In another group of volunteers, the same researcher is now studying how B cells (the immune cells that produce antibodies) respond to COPD patients and how these patients respond to covid-19 vaccines.