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Centre d'Immunologie et des Maladies Infectieuses
UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255

Pathogenesis of Viral Infections and Immune Aging - VICTOR APPAY

Team members

Team Research Program

The work of the team focuses primarily on human and translational research. It involves the study of adaptative and innate immunity in infectious contexts, particularly chronic viral infection (e.g. HIV or CMV), and the decline of immune competence due to aging and inflammation. The study of the aging immune system, or immunogerontology, is a blooming but recent domain of research, and our knowledge of the cellular and molecular changes that underlie the decline in immune function with age remains still limited. A better understanding of the causes and mechanisms of immune aging is therefore a public health priority with crucial implications to optimize care of elderly people, as well as to develop better vaccines for this population.
The work of the team aims to further understand

A./ the causes and consequences of immune resources exhaustion in age or HIV infection, and

B./ the efficacy of T cells to control HIV replication. The knowledge gained from this work is directly relevant to medicine and public health:

  1. Establishing the impact of chronic infections and inflammation in the development of immunosenescence is relevant for our understanding of the mechanisms of immune aging and its consequence on the health of old people, who represent a continuously increasing proportion of our society. Our focus on the importance of primary immune resources has the potential to open new avenues for the development of therapies to compensate or even revert the decline of our immunity with age.
  2. The knowledge gained from this research will provide new insights into the control of HIV replication by T cells and the decline of immune efficacy with the onset of disease progression. This new understanding of what constitutes an effective T cell response in humans and of how it could be induced with potential adjuvants will be directly relevant to strategies aimed at developing successful T cell based vaccines in humans.

Our aims are therefore (i) to provide further mechanistic insights into the exhaustion of immune resources and T cell efficacy in humans, but also and most importantly (ii) to concentrate on ways to valorize this knowledge through the development of potential clinical applications.

Technical expertise

Flow cytometry, Cell culture, Molecular biology

Main achievements

  • We performed the first functional study of HIV-specific CD8+ T cells (Appay, J Exp Med, 2000). We have shown that cellular differentiation in chronic infections differs according to the viral specificity, suggesting for the first time that quite distinct memory T cell populations are established in different virus infections (Appay, Nat Med, 2002). We have highlighted the role of clonotypes with high sensitivity for HIV antigens in controlling HIV replication, identifying clear correlates of CD8+ T cell efficacy against HIV (Almeida, J Exp Med, 2007; Almeida, Blood, 2009; lglesias, Blood, 2011, Ladell, Immunity, 2013).
  • In the field of paralleling HIV infection and immunosenescence, we demonstrated the role of immune activation in the development of premature immune aging (Papagno, PLoS Biol, 2004; Sauce, Blood, 2011). We provided mechanistic insights into the development of immunosenescence demonstrating the synergism between reduced thymic activity and chronic viral infection, in driving exhaustion of T cell resources and repertoire diversity in humans (Sauce, J Clin Invest, 2009).

External funding (current)

At academic level:
ANR  : Immunity and Aging (2014-2018); HIV Vaccine (2014-2018)
ANRS: HIV specific T cell immunity (2016-2017); Inflammation in elderly HIV infected people (2017)
Sidaction : HIV specific T cell (2016-2017)

Publications (PDF):

(2017 - 2016 - 2015 - 2014 - 2013)

20/11/17

Traductions :

Contact

cimi-paris @ upmc.fr

To see

Key words

Virus, infections, Genetic, Epidemiology

Fields of application

T-cell correlates of efficacy in HIV infection, Immune decline with human aging and inflammation, Pathogenesis of viral infections, T-cell based therapy and vaccines.