HMBPP‐deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells. Issue 6 (11th August 2014)

• Record Type: Journal Article
• Authors: Frencher, James T.; Shen, Hongbo; Yan, Lin; Wilson, Jessica O.; Freitag, Nancy E.; Rizzo, Alicia N.; Chen, Crystal Y.; Chen, Zheng W.
• Is Part Of: Journal of leukocyte biology. Volume 96:Issue 6(2014)
• Page Start: 957
• Page End: 967
• Publication Date: 2014-08-11
• Subjects: T cells -- antigen -- cell activation -- memory response -- lung; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.6HI1213-632R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Role for microbial production of phosphoantigen in infection‐driven responses of primate γδ T cells in vivo. Abstract : Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP‐ and IPP‐driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen‐host interplays by comparative immunizations of macaques with the HMBPP/IPP‐coproducing Listeria Δ actA prfA * and HMBPP‐deficient Listeria Δ actA Δ gcpE prfA * mutant. The HMBPP‐deficientΔ gcpE mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP‐producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP‐deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP‐producing vaccine strain. Interestingly, HMBPP‐deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP‐producing listeria. HMBPP‐deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN‐γ and TNF‐α and inhibiting intracellular listeria than HMBPP‐producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention.