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Session 3
Plenary Immune Reconstitution and Immunologic Responses to Antiretroviral Therapies: Implications for Therapeutic Strategies Session Time: Monday, 9 - 9:30 am Room 4B |
Background: The immune system is known for its plasticity. Powerful antiretroviral drugs (HAART) allow partial recovery from the HIV-induced immune alterations by involving complex mechanisms. First the block of virus replication induces a rapid recirculation of preexisting T cells sequestered in tissues, an arrest in the production of inflammatory cytokines and in lymphocyte apoptosis. As a consequence: peripheral blood CD4 cell numbers rapidly increase, being almost exclusively composed of memory cells in AIDS patients and of a mixture of naive and memory cells at earlier stages; functions of memory CD4 T cells directed at opportunistic pathogens progressively recover. Second, a slower but continuous increase in CD4 T cells reflects the recovery in naïve T cells that originated from the thymus and represent a reservoir for memory T cells. The recovery in memory T cells stops the accelerated conversion of naïve T cells towards memory and limit exhaustion while the thymopoiesis progressively recovers, thus ensuring restoration of a diverse T-cell repertoire and normal T-cell numbers in the long term. These responses are achievable at any stage of the disease and ensure host protection against opportunistic infections. Severe limitations exist however since the key immune responses in the control of HIV itself are not restored: the CD4 T cells specific for HIV that had been erased soon after primary infection do not reconstitute, while the preexisting CD8 T cells decrease concurrently to the virus load. Conclusions: Such a phenomenon does not reflect definitive alterations of the immune responses to HIV but rather reflects the insufficient production of HIV antigens during HAART. Such an hypothesis is supported by the rapid rebounds of HIV-specific CD4 and CD8 T cells during virus relapses following treatment discontinuation. This latter strategy is only partially helpful in chronic infection since the rare virus-specific CD4 T cells rapidly disappear in the face of pathogenic virus particles while only preexisting CD8 clones specific for HIV reappear and the immune repertoire does not broaden. Alternative promising strategies are opened by the association of anti-HIV vaccines to HAART in order to restimulate HIV-specific immunity before treatment is stopped, protect the host, and prolong time off therapy. Several programs of therapeutic immunization are in progress using recombinant attenuated pox-viruses or other vaccines. |
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©2002 9th Conference on Retroviruses and Opportunistic Infections |
