Evaluation of non-reciprocal heterologous immunity between unrelated viruses

Jenny, W.; Selin, Liisa K.; Welsh, Raymond M.

doi:10.1016/j.virol.2015.03.002

Cited by 19 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such a situation of preexisting partial immunity to a pathogen can also occur in a primary infection when a pathogen happens to share an epitope with a previously encountered unrelated pathogen—a phenomenon known as heterologous immunity (Welsh et al., 2010, Che et al., 2015). Though highly relevant for understanding immunity in humans, interferences between past and present infections (or vaccinations) are rarely investigated under well-defined conditions.…”

Section: Introductionmentioning

confidence: 99%

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

et al. 2016

View full text Add to dashboard Cite

SummaryMany infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown. We demonstrate that even a minimum epitope overlap between infections strongly increases the activation threshold and narrows the diversity of T cells recruited in response to new antigens. Thus, minimal cross-reactivity between infections can significantly impact the outcome of a subsequent immune response. Interestingly, we found that non-transferrable memory T cells are most effective in raising the activation threshold. Our findings have implications for designing vaccines and suggest that vaccines meant to target low-affinity T cells are less effective when they contain a strong CD8 T cell epitope that has previously been encountered.

show abstract

Section: Introductionmentioning

confidence: 99%

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Other studies on heterologous immunity have shown that when T cell crossreactivity between two pathogens occurs, it may depend on the order of the infection sequence and that it does not necessarily occur in all individuals, due to the private specificity of their TCR repertoires (22,23,64). This was dramatically illustrated in this study where the cross-reactivity was detected only in the MCMVϩLCMV sequence (not LCMVϩMCMV), and when it did occur, it was observed approximately in only one of every five MCMV-immune mice.…”

Section: Discussionmentioning

confidence: 99%

“…with 5 ϫ 10 5 PFU of MCMV or given salivary gland homogenate from naive mice as controls. Memory CD8 T cells specific for GP [33][34][35][36][37][38][39][40][41] , NP 396 -404 , and GP 118 -125 , (a to d) and memory CD4 T cells specific for GP [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] from the spleen (e) were examined at weeks 6, 12, 23, and 48 post-MCMV infection by ICS (n ϭ 5). The complete experiment was done once, but a similar observation was made in a separate experiment in cells harvested at weeks 9 and 24 post-MCMV inoculation.…”

mentioning

confidence: 99%

Heterologous Immunity and Persistent Murine Cytomegalovirus Infection

Jenny

Daniels

Selin

et al. 2017

J Virol

Self Cite

View full text Add to dashboard Cite

One's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. This can occur after acute viral infections, such as infections with lymphocytic choriomeningitis virus (LCMV) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. In this study, murine cytomegalovirus (MCMV) was used as a persistent infection model to study heterologous immunity with LCMV. If mice were previously immune to LCMV and then infected with MCMV (LCMVϩMCMV), they had more severe immunopathology, enhanced viral burden in multiple organs, and suppression of MCMV-specific T cell memory inflation. MCMV infection initially reduced the numbers of LCMV-specific memory T cells, but continued MCMV persistence did not further erode memory T cells specific to LCMV. When MCMV infection was given first (MCMVϩLCMV), the magnitude of the acute T cell response to LCMV declined with age though this age-dependent decline was not dependent on MCMV. However, some of these MCMV persistently infected mice with acute LCMV infection (7 of 36) developed a robust immunodominant CD8 T cell response apparently cross-reactive between a newly defined putative MCMV epitope sequence, M57 [727][728][729][730][731][732][733][734] , and the normally subdominant LCMV epitope L 2062-2069 , indicating a profound private specificity effect in heterologous immunity between these two viruses. These results further illustrate how a history of an acute or a persistent virus infection can substantially influence the immune responses and immune pathology associated with acute or persistent infections with an unrelated virus. IMPORTANCE This study extends our understanding of heterologous immunity in the context of persistent viral infection. The phenomenon has been studied mostly with viruses such as LCMV that are cleared, but the situation can be more complex with a persistent virus such as MCMV. We found that the history of LCMV infection intensifies MCMV immunopathology, enhances MCMV burden in multiple organs, and suppresses MCMV-specific T cell memory inflation. In the reverse infection sequence, we show that some of the long-term MCMV-immune mice mount a robust CD8 T cell cross-reactive response between a newly defined putative MCMV epitope sequence and a normally subdominant LCMV epitope. These results further illustrate how a history of infection can substantially influence the immune responses and immune pathology associated with infections with an unrelated virus. KEYWORDS CD8 T cell, memory inflation, heterologous immunity, cross-reactivity, lymphocytic choriomeningitis virus, murine cytomegalovirus, mouse H eterologous immunity, that is, the ability of immunological memory specific to one pathogen to contribute to the control of a different pathogen, has been an established immunological phenomenon since Edward Jenner used cowpox virus to immunize against variola virus, the cause of human small...

show abstract

“…Of note, HI may alter the immunodominance, induce changes in polarisation or result in loss of speci c T m cells [28]. In addition, heterologous immune responses are not necessarily reciprocal [40].…”

Section: Heterologous Immunitymentioning

confidence: 99%

Respiratory virus-induced heterologous immunity

2018

View full text Add to dashboard Cite

Purpose: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. Methods: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratoryvirus induced adaptive HI. Results: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and in uenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines, which have the potential Cite this as Pusch E, Renz H, Skevaki C. Respiratory virus-induced heterologous immunity -Part of the problem or part of the solution? Allergo J Int 2018; 27:79-96

show abstract

Evaluation of non-reciprocal heterologous immunity between unrelated viruses

Cited by 19 publications

References 42 publications

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

Heterologous Immunity and Persistent Murine Cytomegalovirus Infection

Respiratory virus-induced heterologous immunity

Contact Info

Product

Resources

About