Persistent memory CD4+ and CD8+ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen

Abstract

The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-γ) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4+ and CD8+ T cells were involved in cellular responses to SARS-CoV M antigen. Furthermore, memory CD8+ T cells displayed an effector memory cell phenotype expressing CD45RO− CCR7− CD62L−. In contrast, the majority of IFN-γ + CD4+ T cells were central memory cells with the expression of CD45RO+ CCR7+ CD62L−. The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV M protein identified four human T-cell immunodominant peptides, p21-44, p65-91, p117-140 and p200-220. All four immunodominant peptides could elicit cellular immunity with a predominance of CD8+ T-cell response. This data may have important implication for developing SARS vaccines.

Characterization of γδ T cell subsets in organ transplantation

“…The terminally differentiated phenotype exhibited by Vd1 T cells in transplant recipients parallels the phenotypic characteristics of effector memory RA ab CD8+ T cells (T EMRA ) [23] found in the context of persistent viral infections [24]. While we lack data on the specificity of the expanded cd T cells for our patients, their phenotypic traits are very similar to expanded cd T cell subset, CMV specific, recently identified in kidney recipients [25].…”

Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus

“…A recent study using MA15-infected mouse models suggested that age-dependent increases of prostaglandin D2 expression in the lung may be associated with impaired immune response (Zhao et al, 2011). Retrospective analyses of recovered SARS patients suggests that patients who recovered from SARS possessed specific acquired immunity based on both T and B cells (Yang et al, 2006(Yang et al, , 2007Li et al, 2008;Fan et al, 2009). Notably, most patients who recover from SARS had elevated and sustained levels of neutralizing Abs, and patients with longer illnesses exhibited lower levels of neutralizing Abs than did patients with shorter durations of illness (Temperton et al, 2005;Ho et al, 2005).…”

“…The development of an effective treatment strategy for SARS cases will require clarifying the precise mechanisms by which host immune responses control SARS-CoV infection. Cumulative evidence suggests that patients who recovered from SARS possessed specific acquired immunity based on both T and B cells (Yang et al, 2006(Yang et al, , 2007Li et al, 2008;Fan et al, 2009). However, the effector cells or molecules that act to eliminate SARS-CoV during the acute phase of the infection remain unclear.…”

T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV

“…Although whether the memory T-cell response is sufficient to protect from reinfection requires further investigation, it has been suggested that a more robust CTL response contributes to protection against SARS-CoV in mice Chen et al, 2010a;Zhao et al, 2010a). 2009; Peng et al, 2006;Yang et al, 2006Yang et al, , 2007. Unlike waning serum antibody levels in patients, CTL responses against the S and N proteins can still be detected from the PBMCs of recovered SARS patients 1, 2, 4, 6, and even >10 years post-infection (Da Guan et al, 2015;Ng et al, 2016;Oh et al, 2011;Tang et al, 2011).…”