FLOW CYTOMETRIC CHARACTERIZATION OF THE FALSE NAIVE (CD45RA-, CD29 BRIGHT+) PERIPHERAL-BLOOD T-LYMPHOCYTES IN HEALTH AND IN RHEUMATOID-ARTHRITIS(, CD45RO)

The aim of this study was to quantify and characterise the CD4+ and CD 8+, CD45RA+, CD45RO- T-lymphocytes that paradoxically expressed the CD 29 bright+ phenotype in health and in rheumatoid arthritis. We further evaluated their clinical implications. Blood samples were obtained fr om 100 patients with rheumatoid arthritis and 40 age- and sex-matched controls. Cell surface antigens and interleukin-2 (IL-2) binding were detected on CD4+ and CD8+ peripheral blood T-lymphocytes (T-PBL) by th ree-colour flow cytometry. One-third of the patients were clinically e valuated at the time of blood sampling. In healthy donors, we found 16 +/-14% of CD29 bright+ cells among CD4+, CD45RA+, RO- T-PBL. These ''f alse naive'' CD4+ T-PBL were Leu-8+, and a majority expressed the CD25 /p55 receptor (IL-2R alpha chain), while a minority showed the CD11a b right+, CD69+ and/or CD122/p75+ (IL-2R beta chain) phenotype, and few cells were CD31 bright+ and HLA-DR+. In rheumatoid arthritis, their pr oportion among CD4+, CD45RA+, RO- cells increased to 25+/-15% (P<0.001 , compared with controls). In patients, the reductions in CD31 and CD3 8 expression (P<0.05 for both), as well as the enhanced CD25 expressio n (P<0.001) on CD4+, CD45RA+, RO- T-PBL reflected a more differentiate d phenotype. The occurrences of CD25 and CD122 were increased on false naive CD4+ T-PBL (0.01<P<0.001); however, the binding of IL-2 remaine d very low (in contrast to the binding of IL-2 on CD45RO+ T-PBL). Furt hermore, a major subset of CD8+, CD45RA+, RO- T-PBL (45+/-17% in contr ols) expressed the CD29 bright+ phenotype. These ''false naive'' CD8T-PBL included a great many of CD11b+, CD28- cells, while a minority s howed the HLA-DR+, CD69+ and/or CD122+ phenotypes. Patients with low l evels of IgM rheumatoid factors (IgM-RF; but with active disease) had an elevated proportion of CD45RA+, RO- cells among the CD8+ T-PBL, in part due to an increased proportion of false naive cells (P<0.05). In patients, the false naive CD8+ T-PBL showed down-regulated CD11b and a n increased expression of IL-2 receptor chains (CD25 and CD122; 0.05<P <0.01), but without a significant increase in IL-2 binding. More CD69 on false naive CD8+ T-PBL was found in patients with high levels of Ig M-RF (P<0.005 compared to patients with low IgM-RF). Finally, both fal se naive CD4+ and CD8+ T-PBL correlated with the clinical process and outcome variables (0.05<P<0.01). The levels of activated false naive C D4+ T-PBL (CD25+ and/or CD122+) or CD8+ T-PBL (CD69+ and/or CD122+) we re associated with clinical parameters of disease activity (0.05<P<0.0 1). Thus, in rheumatoid arthritis, false naive T-PBL showed important qualitative differences. The levels of activated false naive T-PBL cou ld be particularly interesting for monitoring disease evolution.