Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Abstract

Combination antiretroviral therapies (cART) can lead to normal life expectancy in HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV group. Although HIV and aging are independently associated with impaired humoral immunity, immune status in people aging with HIV is relatively unexplored. In this study influenza vaccination was used to probe age associated perturbations in the B cell compartment of HIV-negative “healthy controls” (HC) and virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped by age as young (<40 yrs), middle-aged (40-59yrs) or old (≥60 yrs). H1N1 antibody response at d21 post-vaccination correlated inversely with age in both HC and HIV. Immunophenotyping of cryopreserved PBMC demonstrated increased frequencies of double negative B cells and decreased plasmablasts in old compared to young HC. Remarkably, young HIV were different from young HC but similar to old HC in B cell phenotype, influenza specific spontaneous (d7) or memory (d21) antibody secreting cells. We conclude that B cell immune senescence is a prominent phenomenon in young HIV in comparison to young HC, but distinctions between old HIV and old HC are less evident though both groups manifest age-associated B cell dysfunction.

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…findings that functional defects in pTfh cells present prior to vaccination in HIV-infected individuals on cART contribute to poor vaccine-induced Ab production (38,50) and support peripheral Tfh cells as a promising biomarker for assessing immune function and potential for Ab response in response to vaccination. The PD-1/PD-L1 signaling axis between T/B cells has recently been implicated in dysregulated B cell function and Ab response to TIV by our group (28). Indeed, the finding of PD-1, an immune checkpoint molecule, as a predictive marker on pTfh provides a potential target for intervention given the therapeutic successes of checkpoint-inhibitor drugs, and strategies targeting this pathway may lead to improved immune function in HIV + individuals.…”

T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection

“…Interestingly the young HIV + showed maximum variance from HIV − and more rapid decay in titer after peak at 28 days postvaccination. In statistical analysis somewhat surprisingly effect of age rather than HIV dominated the impaired immune response observed in old persons (age > 60 years), whereas HIV clearly had a strong effect on immunity at younger ages ( 99 , 100 ).…”

“…To examine the role of age and HIV infection further, we are engaged in a large ongoing study ( 99 , 100 ) in virologically suppressed HIV + and HIV − adults grouped by age as young (<40 years), middle aged (40–59 years), and old (≥60 years). Following seasonal trivalent influenza vaccine (TIV), magnitude of Ab titers against each vaccine strain were found to be lower in old age compared to others, regardless of HIV status.…”

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

“…Serum antibody responses postvaccination showed the best responses (frequency and magnitude) in young uninfected participants, whereas a high proportion of old uninfected participants, as well as PWH of all age groups, were vaccine nonresponders (VNR). 49 Defects of B cells 50 and monocyte/macrophages 51 and association of inflammation and immune activation with VNR status 52 were also described. Interestingly, there was also a profound deficiency of influenza-specific and total peripheral T follicular helper (pTfh) cells in VNR and their pTfh cells exhibited markers of immune activation.…”