Background/Purpose: Zwitterionic polysaccharides can activate CD4+ T cells after processing and presentation by antigen-presenting cells. The 23-valent capsular polysaccharide pneumococcal vaccine, PneumoVax, protects against invasive pneumococcal pneumonia and is indicated for patients with chronic autoimmune diseases and/or on chronic immunosuppressive treatment. The effect of polysaccharide vaccines on the function of cellular immunity and the inflammatory response are not well defined. We studied the immunological effects of pneumococcal polysaccharide vaccination in the MRL/lpr mouse model of lupus, by analyzing the cytokine profile of activated T and B lymphocytes. We also analyzed the effect of polysaccharide vaccination on the expression of Stat1 in the kidney and brain, target organs of inflammation in this mouse model of lupus.

Methods: Eight week old MRL/lpr mice were purchased from Jackson Laboratories. The first group of mice (n=5) vaccinated with PneumoVax (0.5ml of a 23-valent unconjugated pneumococcal polysaccharide vaccine), the second group (n=5) received Mycophenolate mofetil (MMF) (100mg/kgr of body weight) in standard mouse chow, and the third group (n=5) was left untreated. Eight weeks after treatment the mice were sacrificed. T and B lymphocytes were isolated from the spleens. T cells were stimulated with soluble CD3/CD28 beads, PHA and plate bound polysaccharides. B lymphocytes were stimulated with plate bound IgM, plate bound polysaccharide, LPS and a R848. The culture supernatants of the stimulated lymphocytes were analyzed by specific ELISAs for cytokine production of IL-4, IFN-g, IL-17, IL-10, TNF-a and IL-6. Protein extracts were isolated from perfused kidneys. Stat1 and Stat3 protein levels from the extracts were analyzed with Western blotting.

Results: T lymphocytes from PneumoVax vaccinated mice showed differential regulation of cytokine production after CD3/CD28 stimulation, with complete block in IFN-g and IL-17 production compared with the non-vaccinated mice. CD3/CD28-induced IL-4 and TNF production by T cells did not differ in the two groups; however, IL-10 production was significantly increased in the vaccinated group. Interestingly, the decrease in T cell IFN-g and IL-17 production was comparable to the MMF treated group. B lymphocytes from PneumoVax vaccinated mice produced significantly decreased IL-6, IL-10 and TNF in response to plate bound IgM, LPS and R848 stimulation compared to the control group. Analysis of Stat1 protein levels in the kidneys, showed that PneumoVax vaccinated mice had significantly decreased expression compared with the control group, whereas Stat3 levels were not affected.

Conclusion: Pneumococcal polysaccharide vaccination preferentially modulates T and B lymphocyte cytokine responses, after antigen and pattern recognition receptor stimulation in the MRL/lpr mouse model of lupus. Moreover, the expression of Stat1 in the kidneys, a major target organ of inflammation in this model, was significantly decreased in the polysaccharide vaccinated animals. These results suggest that zwitterionic polysaccharides may have a role in re-establishing the immune and inflammatory homeostasis in chronic autoimmune/inflammatory conditions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pneumococcal-polysaccharide-vaccination-regulates-t-and-b-lymphocyte-cytokine-responses-and-decreases-kidney-stat1-levels-in-mrllpr-mice-in-vivo/