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ANDREA COOPER, PH.D.
Chronic infection in the elderly.

The function of the immune system changes profoundly with age. One of the most clinically important changes is that vaccine efficacy significantly declines in the elderly, leaving them more susceptible to infectious diseases such as influenza and pneumonia. This decline leads to lower overall antibody (Ab) titers as well as reduced Ab function, when compared to younger individuals. Studies of our colleague (Dr Haynes), using a novel adoptive transfer model with T cell receptor transgenic (TCR Tg) CD4 T cells, have shown that naive CD4 T cells from aged individuals exhibit reduced cognate helper function when compared to cells from young donors, regardless of the age of the adoptive host. It is this cognate helper function of CD4 T cells that is vital for the induction of potent antibody responses. The aged host therefore has an intrinsic defect in T cell function that contributes to the reduced efficacy of the acquired immune response.

A further confounding factor with the potential to impact the primary immune response to vaccination is the fact that aging individuals have an increased incidence of inflammation and chronic inflammatory infection. We have discovered that aged hosts express an increased frequency of cells capable of producing the inflammatory cytokine IL-17 and that this frequency is further increased by the presence of mycobacterial infection. In combining these observations we were prompted to propose the following hypothesis: that the priming and cognate function of CD4 T cells is influenced by chronic infection and that age of both T cells and host exacerbates this influence. The hypothesis raises several questions. The first is whether the presence of a chronic inflammatory infection in an aged host can impact the priming of competent T cells. The second is whether aged T cells are impacted by the increased inflammation associated with infection of the aged host. The third is whether the chronic inflammation associated with infection in the aged host impacts the ability of aged CD4 T cells to provide cognate help to B cells. The fourth is whether infection is able to impact the induction and expression of vaccine-induced memory responses in the aged host.

We are currently addressing these questions.



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ROBERT NORTH, PH.D. MARCIA A. BLACKMAN, PH.D. TIMOTHY SELLATI, PH.D. MARKUS MOHRS, PH.D. MITHILESH JHA, PH.D. LAWRENCE L. JOHNSON, PH.D. ANDREA COOPER, PH.D. ALEXEI TUMANOV, M.D., PH.D. ELIZABETH LEADBETTER, PH.D. SUSAN L. SWAIN, PH.D. RICHARD W. DUTTON, PH.D. DAVID WOODLAND, PH.D. GARY WINSLOW, PH.D. LAURA HAYNES, PH.D. WILLIAM W. REILEY, PH.D. JR-SHIUAN LIN, PH.D. RON GOLDFARB, PH.D.