AGE-RELATED CHANGES IN THE ABSOLUTE NUMBER OF CD95 POSITIVE CELLS IN T CELL SUBSETS IN THE BLOOD RICHARD ASPINALL, 1 JENNIFER CARROLL, 2 and SHISONG JIANG 3 1 Department of Immunology, Chelsea & Westminster Hospital, London SW10 9NH, UK, 2 Department of Medicine for Elderly People, Whipps Cross Hospital, Leytonstone, London UK, and 3 Department of Infections and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK Abstract—Comparison of the absolute number of cells in distinct T cells subsets expressing CD95 (Fas) was carried out in two populations of healthy female volunteers. In one population, the average age was 30  5 years, and in the second population the average age was 73  13 years. No significant difference was noted in the total number of lymphocytes, CD3 + , CD4 + , or CD8 + cells per L of blood between the two age groups, but major differences were noted in the number of cells expressing CD95. A significant reduction was seen in the number of cells per L of blood in both the CD4 + CD45RA + CD95 + and CD8 + CD45RA + CD95 + populations in the older group compared with the younger group. Within the memory pool significantly fewer CD8 + CD45RO + CD95 + cells were found in the older population compared with the younger group. No such difference were found in the number of CD4 + CD45RO + CD95 + cells between groups. Such a significant decline in the number of CD95 + cells, whose expression is known to be linked with activation, may be implicated as a mechanism by which cells that have reached a stage of replicative senescence remain in the peripheral T cell pool. Anti-CD3–mediated activation of cells from both groups revealed much lower proliferative responses from the older group, supporting the idea that there is an age-associated increase in the number of cells that have reached their replicative limit. These cells may not be lost from the peripheral pool because they fail to express CD95. © 1998 Elsevier Science Inc. Key Words: aging, CD95, replication limit, lymphocyte subsets, activation INTRODUCTION CD95 (FAS/APO-1) is a 45 kDa cell surface protein belonging to the TNF receptor family, which is expressed on a variety of cells including cells of the lymphocyte lineage. Crosslinkage of the CD95 molecule, either by antibody, or its ligand (CD95L) results in the generation of an Correspondence to: R. Aspinall, Dept. of Immunology, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. Tel: +44-181-746-5993; Fax: +44-181-746-5997; E-mail: r.aspinall@ic.ac.uk (Received 5 March 1998; Accepted 13 May 1998) Experimental Gerontology, Vol. 33, No. 6, pp. 581–591, 1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0531-5565/98 $19.00 + .00 PII S0531-5565(98)00035-7 581