The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice

Yufei Wang, Durdana Rahman, Mukesh Mistry, Thomas Lehner

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Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K(+) efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant. The aims of this study are to extend these investigations to T and B cell responses of unimmunized and ovalbumin (OVA)-immunized BALB/c mice, and furthermore, to ascertain whether stress is involved in optimal expression of memory B cells, as demonstrated in CD4(+) T cells. Examination of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome pathway defined by the IL-1-IL-1R interaction between dendritic cells (DC) and CD4(+) T cells suggests that both pathways are involved in the development of optimal expression of CD4(+)CD45RO(+) memory T cells in unimmunized and OVA-immunized BALB/c mice. Furthermore, significant direct correlation was found between CD4(+)CD44(+) memory T cells and both IL-15 of the homeostatic and IL-1β of the inflammasome pathways. However, CD19(+)CD27(+) memory B cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the proliferative responses are enhanced by the stress agents. Altogether, stress agents may up-regulate unimmunized and OVA-immunized CD4(+)CD44(+) memory T cells by the homeostatic and inflammasome pathways. However, the CD19(+)CD27(+) memory B cells utilize only the homeostatic pathway.

Original languageEnglish
Pages (from-to)20707-17
Number of pages11
JournalJournal of Biological Chemistry
Issue number39
Early online date8 Aug 2016
Publication statusPublished - 23 Sept 2016


  • Animals
  • Antigens, CD19
  • Antigens, CD27
  • Antigens, CD44
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Immunization
  • Immunologic Memory
  • Interleukin-15
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Receptors, Interleukin-1
  • Stress, Physiological
  • Journal Article


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