Altered CD4+ T cell immunity in nurses occupationally exposed to viral pathogens

Abstract

Pathogen exposure, including but not limited to herpesviruses, moulds the shape of the immune system, both at a basal state and in response to immune challenge. However, little is known about the impact of high exposure to other viruses on baseline immune signatures and how the immune system copes with repetitive exposures to maintain a balanced functionality. Here we investigated baseline immune signatures, including detailed T cell phenotyping, antigen-specific CD4 and CD8 T cell responses and cytokine profile in paediatric (PED) nurses, who have high occupational exposure to viral pathogens including varicella zoster virus (VZV) and respiratory viruses, and in neonatal intensive care unit (NICU) nurses, as a control group with infrequent occupational exposure. Our results show a lower CD4 T cell response to two VZV proteins (IE62 and gE) and to tetanus toxoid (TT) in PED nurses who are cytomegalovirus (CMV)-seronegative, compared to CMV-seronegative NICU nurses, and that the decline might be more pronounced the more sustained the exposure. This decline might be due to an attrition of VZV- and TT-specific T cells as a result of the continuous pressure on the CD4 T cell compartment. Moreover, our data suggest that the distinct T cell phenotypes known to be associated with CMV-seropositivity might be less prominent in PED nurses compared to NICU nurses, implying a plausible attenuating effect of occupational exposure on CMV-associated immunosenescence. Overall, this pilot study reveals an impact of occupational exposure to viral pathogens on CD4 T cell immunity and supports further investigation in a larger cohort.

Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations

“…Healthy serum samples were collected at a single time point from 40 neonatal intensive care unit or pediatric unit nurses. 36 Recruited subjects were 100% White/Caucasian. Inclusion criteria included a minimum of two years working in the respective hospital unit, a maximum of one year between blood sampling and last VZV exposure for pediatric unit nurses, and a minimum of one year between blood sampling and last VZV exposure for neonatal intensive care unit nurses.…”

“…To begin assessing baseline immune status, the levels of 38 plasma/serum cytokines were measured in 631 healthy subjects. [33][34][35][36][37][38] Cytokine levels were natural log (ln) transformed and visualized using a t-Distributed Stochastic Neighbor Embedding (t-SNE) plot which aids in dimensionality reduction while utilizing data from all cytokines measured. These results show marked variation in cytokine levels, with distinct clustering by cohort.…”

Sequential Immunization With Heterologous Viruses Does Not Result in Attrition of the B Cell Memory in Rainbow Trout

“…In a pivotal report published in 2004 (4), Selin et al showed selective loss of LCMV-specific memory CD8 + T cells after sequential infections with heterologous viruses (5). Altered CD4 + responses have also been reported, for example in nurses frequently exposed to viral pathogens (6). Two models have been proposed to explain T cell attrition.…”