Eradication of clonally expanded CD4+ T cells

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Project Summary Clonal expansion is a process where latently infected CD4+ T cells proliferate in response to their cognate antigen. It is thought that this process contributes significantly to the size of the HIV reservoir and therefore disrupting this mechanism could have a huge impact on the number of latently infected cells. We observed a significant decline in the number of expanded CD4+ T cell clones in an elite suppressor who received chemoradiation for lung cancer and we hypothesize that we can recapitulate this in vitro by stimulating CD4+ T cells with a combination of cognate antigen to induce proliferation, and either chemotherapeutic or antiproliferative agents that would selectively kill the dividing antigen-specific CD4+ T cells. If successful, a two-step process of vaccination of individuals with cognate antigen and short term treatment with chemotherapeutic or antiproliferative agents may be part of a strategy to reduce the size of the reservoir.