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A new target for HIV vaccine: the critical role of an NKp44 ligand in the CD4+ T depletion by NK cells in SHIV162P3 infected macaques
Presented by Patrice Debre, France.
Vieillard V.1, Le Grand R.2, Debre P.1
1INSERM U543, Hôpital Pitié-Salpêtrière, Paris, France, 2CEA, Fontenay-aux-roses, France
Objectives: HIV infection leads to a state of chronic immune activation and progressive deterioration in immune function, manifested most recognizably by the progressive depletion of CD4+ T cells. Recently, we have shown that a cellular ligand for the NCR NKp44 (NKp44L) is expressed during HIV-1 infection and is correlated with both the progression of CD4+ T cell depletion and the increase of viral load. The ligand´s expression is strongly induced by a highly conserved motif of the HIV-1 envelope gp41 protein, called 3S.
Methods: Ten Macaques were either immunized with 3S-KLH or KLH alone and then infected with SHIV162P3. Blood samples were collected each week up to day 42. Cell surface expression of NKp44L was analyzed using flow cytometric analysis, the engagement of NKp44L during the NK lysis process was evaluated using a standard 51Cr release assay, and the level of anti-3S antibodies production was detected by ELISA in the serum samples.
Results: All animals immunized with 3S-KLH developed a strong immune response against 3S, whereas the animals immunized with KLH alone did not. After SHIV infection, CD4+ T cells depletion increased with time in control animals. By contrast, anti-3S immunization inhibits CD4+ T cells death, and the subsequent CD4 cells decline, without affecting viral replication. In support of our hypothesis, anti-3S immunization suppresses NKp44L on CD4+ T cells, and then prevented the NK lysis activities.
Conclusions: These data which indicate that NK cells may have a deleterious role on CD4+ T cells, and explain, at least partially, their depletion, raise new questions about the pathogenesis of HIV and present new opportunities for HIV vaccine strategies based on 3S immunization.
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