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Lack of Antibody Production Following Immunization in Old Age: Association with CD8⁺CD28^- T Cell Clonal Expansions and an Imbalance in the Production of Th1 and Th2 Cytokines¹

Maria Saurwein-Teissl^*, Thomas L. Lung^*, Florentine Marx^*, Claudio Gschösser^*, Esther Asch^*, Imrich Blasko^*, Walther Parson, Günther Böck, Diether Schönitzer, Emanuelle Trannoy^¶ and Beatrix Grubeck-Loebenstein^2,*

^* Institute for Biomedical Aging Research of the Austrian Academy of Sciences, and Institute of Legal Medicine, Institute of Pathophysiology, Central Institute for Blood Transfusion, University Clinics Innsbruck, Innsbruck, Austria; and ^¶ Aventis-Pasteur, Marcy l’Etoile, France

Although it is generally recognized that the function of the immune system declines with age, the nature of the underlying defects is still poorly understood. We now demonstrate the predominance of CD8⁺CD28^- T cell clonal expansions in elderly persons who fail to produce specific Abs following influenza vaccination. These clones express effector cell markers and are mostly CD45RA⁺. When isolated and put into culture, they are unable to proliferate, but produce IFN- (but no IL-5) upon stimulation with anti-CD3 or autoantigen. These autoreactive CD8⁺ type 1 effector cells seem to trigger a Th1 polarization, as CD4⁺ T cells from elderly persons without in vivo Ab production produce Th1, but only low amounts of Th2 cytokines upon in vitro stimulation with PHA. Therefore, the increased occurrence of CD8⁺CD28^- clonal expansions may be decisive for the development of immune deficiency in the elderly.

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