Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV) in healthy subjects

Abstract

Respiratory syncytial virus (RSV) is the major pathogen causing respiratory disease in young infants and it is an important cause of serious illness in the elderly since the infection provides limited immune protection against reinfection. In order to explain this phenomenon, we investigated whether healthy adults of different age (20-40; 41-60 and > 60 years), have differences in central and effector memory, RSV-specific CD8+ T cell memory immune response and regulatory T cell expression status. In the peripheral blood of these donors, we were unable to detect any age related difference in term of central (CD45RA-CCR7+) and effector (CD45RA-CCR7-) memory T cell frequency. On the contrary, we found a significant increase in immunosuppressive regulatory (CD4+25+FoxP3+) T cells (Treg) in the elderly. An immunocytofluorimetric RSV pentamer analysis performed on these donors' peripheral blood mononuclear cells (PBMCs), in vitro sensitized against RSV antigen, revealed a marked decline in long-lasting RSV specific CD8+ memory T cell precursors expressing interleukin 7 receptor α (IL-7Rα), in the elderly. This effect was paralleled by a progressive switch from a Th1 (IFN-γ and TNF-α) to a Th2 (IL-10) functional phenotype. On the contrary, an increase in Treg was observed with aging. The finding of Treg over-expression status, a prominent Th2 response and an inefficient RSV-specific effector memory CD8+ T cell expansion in older donors could explain the poor protection against RSV reinfection and the increased risk to develop an RSV-related severe illness in this population. Our finding also lays the basis for new therapeutic perspectives that could limit or prevent severe RSV infection in elderly.

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

“…In contrast, clinical studies indicate that old humans express similar or even higher titers of RSV-specific IgG antibodies (28,31,39,41). However, several of those studies indicate that the functionality of these antibodies is inferior compared to that of the antibodies of younger people (28,39). Of note, old humans have been exposed more often to RSV infection during their lifespan than young people.…”

“…The capacity to generate antibodies in response to vaccination and infection is reduced at old age (24)(25)(26)(27)(28). To assess whether this age effect is paralleled in the cotton rat model, we compared the production of antibodies in response to HRSV vaccine in young cotton rats to that in old cotton rats.…”

“…Besides antibodies, T cells are important for an effective immune response required to clear virus. Since functionality and numbers of RSV-specific CD4 ϩ and CD8 ϩ T cells drop with age (28,44,45), it would be useful to unravel how T-cell responses at old age are involved in the induction of protective immunity by RSV vaccines and how these responses can be improved to act in concert with antibodies to achieve protection at old age.…”

“…However, the relationship between antibody levels induced by HRSV and age in humans is still subject to speculation. Observations on the effect of age on the immune response to vaccine may be blurred since social behavior, environment, frailty, and a varying history of natural infections can influence the outcome of human studies (25,28,32,(37)(38)(39)(40). To clarify the effect of aging on the capacity to mount antibody production in response to HRSV vaccine, we analyzed the antibodies produced in response to vaccination with rHRSV, which induced suboptimal protection in old animals but fully protected young cotton rats.…”

Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

“…It is known that elderly individuals display impaired T cell immune responses and this likely contributes to the frequency of respiratory syncytial virus reinfection. 18 In fact, immunosenescence is an important factor predisposing to infection in elderly individuals. 19 Consistently, we documented in 8 of 58 elderly patients who had been studied immunologically, a lower type 1 immune response and an increase in IL-10 production upon stimulation with SLA.…”