Changes in peripheral blood lymphocyte subsets in elderly subjects are associated with an impaired function of the hypothalamic /pituitary  /adrenal axis Victor Martı ´nez-Taboada a,b, *, Marı ´a Jose ´ Bartolome ´ b , Jose ´ Antonio Amado c , Ricardo Blanco a , Maria Teresa Garcı ´a-Unzueta c , Vicente Rodrı ´guez-Valverde a , Marcos Lo ´ pez-Hoyos b a Services of Rheumatology, Immunology, and Endocrinology, Santander, Spain b Hospital Universitario Marque ´s de Valdecilla, 39008 Santander, Spain c Facultad de Medicina, Universidad de Cantabria, Santander, Spain Received 10 May 2002; received in revised form 17 July 2002; accepted 9 September 2002 Abstract A growing body of evidence indicates that ageing brings a progressive disruption in the immune and endocrine systems. However, very few reports have correlated the changes in the immune system with the endocrine function in the elderly. The aim of the present study was to investigate the changes occurring in the peripheral blood lymphocyte subpopulations with age and correlate them with the hypothalamic  /pituitary  /adrenal (HPA) function. We determined the peripheral blood lymphocyte phenotype and the T cell receptor usage by flow cytometry analysis. The HPA function was evaluated by the basal serum levels of adrenal steroids and the response to stimulation with a low-dose ACTH. In the elderly, we observed a decrease of major T subsets together with an increase of NK cells and activated T cells. With regard to the HPA function, the most significant decline was found in dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS). A close correlation between immune changes with ageing and DHEA response to ACTH stimulation was found. The present study showed an inverse correlation of lymphocyte changes with the plasma levels of steroids, especially DHEA and its metabolite, DHEAS. This association was not found for other steroids and points for the possibility of using DHEA to correct the immunological decline associated with ageing. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ageing; Lymphocyte subsets; HPA axis; DHEA; T cell expansions 1. Introduction Ageing is accompanied by a number of quanti- tative and qualitative changes in the immune response which are grouped by the term of immunosenescence (Pawelec and Solana, 1997). * Corresponding author. Tel./fax:  /34-942-20-3453 E-mail address: inmlhm@humv.es (V. Martı ´nez-Taboada). Mechanisms of Ageing and Development 123 (2002) 1477 /1486 www.elsevier.com/locate/mechagedev 0047-6374/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0047-6374(02)00116-1