July 26, 2019 Journal article Open Access

Castiglione, Filippo; Ghersi, Dario; Celada, Franco

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{
  "DOI": "10.3389/fimmu.2019.01513", 
  "container_title": "Frontiers in Immunology", 
  "language": "eng", 
  "title": "Computer Modeling of Clonal Dominance: Memory-Anti-Na\u00efve and Its Curbing by Attrition", 
  "issued": {
    "date-parts": [
      [
        2019, 
        7, 
        26
      ]
    ]
  }, 
  "abstract": "<p>Experimental and computational studies have revealed that T-cell cross-reactivity is a&nbsp;widespread phenomenon that can either be advantageous or detrimental to the host.&nbsp;In particular, detrimental effects can occur whenever the clonal dominance of memory&nbsp;cells is not justified by their infection-clearing capacity. Using an agent-based model&nbsp;of the immune system, we recently predicted the &ldquo;memory anti-na&iuml;ve&rdquo; phenomenon,&nbsp;which occurs when the secondary challenge is similar but not identical to the primary&nbsp;stimulation. In this case, the pre-existingmemory cells formed during the primary infection&nbsp;may be rapidly deployed in spite of their low affinity and can actually prevent a potentially&nbsp;higher affinity na&iuml;ve response from emerging, resulting in impaired viral clearance. This&nbsp;finding allowed us to propose a mechanistic explanation for the concept of &ldquo;antigenic&nbsp;sin&rdquo; originally described in the context of the humoral response. However, the fact&nbsp;that antigenic sin is a relatively rare occurrence suggests the existence of evolutionary&nbsp;mechanisms that can mitigate the effect of the memory anti-na&iuml;ve phenomenon. In&nbsp;this study we use computer modeling to further elucidate clonal dominance and the&nbsp;memory anti-na&iuml;ve phenomenon, and to investigate a possible mitigating factor called&nbsp;attrition. Attrition has been described in the experimental and computational literature&nbsp;as a combination of competition for space and apoptosis of lymphocytes via type-I&nbsp;interferon in the early stages of a viral infection. This study systematically explores&nbsp;the relationship between clonal dominance and the mechanism of attrition. Our results&nbsp;suggest that attrition can indeed mitigate the memory anti-na&iuml;ve effect by enabling the&nbsp;emergence of a diverse, higher affinity na&iuml;ve response against the secondary challenge.<br>\nIn conclusion, modeling attrition allows us to shed light on the nature of clonal interaction&nbsp;and dominance.&nbsp;</p>", 
  "author": [
    {
      "family": "Castiglione, Filippo"
    }, 
    {
      "family": "Ghersi, Dario"
    }, 
    {
      "family": "Celada, Franco"
    }
  ], 
  "volume": "10", 
  "type": "article-journal", 
  "id": "3351968"
}