Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus

Abstract

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, Ld-IL2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, Ld-IL2 treatment exacerbated CD8+ T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid the potential risk of CD8+ T cell-mediated immunopathology in severe infections.

Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

“…Since these cells function in anti-viral and anti-bacterial defence 56 , our findings suggest a role of IL-2 immunotherapy in the recruitment of MAIT and V γ9 V δ2 T cells to tissues following treatment, thereby increasing defence against viral and bacterial infections 57 . This could provide a mechanism for the observed decreased incidence of viral infections in SLE patients undergoing LD-IL-2 immunotherapy 58 .…”

Protein vaccine NVX-CoV2373 elicits functional T cell immunity

“…Conventionally, protein vaccines do not have a record as good inducers of CD8 + T cell responses, as compared with live-attenuated or inactivated vaccines ( 17 ). With pathogens that are less vulnerable to antibody-mediated protection, such as Listeria monocytogenes , or are highly mutating, such as flu virus, CD8 + T cells play a critical role in providing protective immunity ( 18 ). mRNA vaccines and natural infections induce robust memory CD8 + T cell responses that cross-recognize SARS-CoV-2 variants, including Omicron ( 19 ).…”

Dilemma of immunosuppression and infection risk in systemic lupus erythematosus

“…An increased incidence of sepsis was observed among patients with higher disease activity. A recent real-world study also showed that the most common infection site is the respiratory system, followed by the skin and urinary system, while bacteria, viruses and fungi are the most common pathogens [ 15 ]. Similar trends were found in a previous study [ 13 ].…”

“…MTX, Ld-IL2 and HCQ) are considered to be safe in SLE patients in terms of not increasing infection risk, and Ld-IL2 therapy has emerged as a new therapeutic option in a variety of autoimmune diseases, aiming to reduce the risk of infection ( Fig. 2 , Table 1 ) [ 15 , 61–65 ]. It has been suggested that Ld-IL2 improves the immune response to the hepatitis-B vaccine in uremic patients [ 66 ].…”