DIFFERENTIAL EXPRESSION OF CYTOKINE GENES IN CD27-POSITIVE AND CD27-NEGATIVE CD4 LYMPHOCYTE SUBSETS FROM HEALTHY HUMANS AND RHEUMATOID-ARTHRITIS PATIENTS

Immunofluorescence analysis of CD27 expression by CD4 lymphocytes from the peripheral blood of healthy humans or rheumatoid arthritis (RA) p atients and from the synovial fluid (SF) of RA patients was carried ou t along with the estimation of cytokine gene [interleukin (IL) 2, IL-3 , IL-4, IL-5, IL-6, IL-6R, IL-10 and interferon-gamma (IFN-gamma)] exp ression in these lymphocyte subsets by RT-PCR. Although no differences in CD27-positive and -negative peripheral blood CD4 cell subset distr ibution were revealed, marked differences in IL-3, IL-4, IL-5 and IFN- gamma mRNA expression were detected between these lymphocyte subsets a nd between control and disease states. These results showed that pheno typing of different cell subsets in disease cannot provide adequate in formation about lymphocyte functional status. To estimate differences in cytokine gene expression, CD4 lymphocytes from the peripheral blood and SF of RA patients were compared. In both cases, mRNAs for IL-2, I L-4, IL-10 and IFN-gamma were detected, but CD4 cells from SF failed t o express detectable levels of IL-5 mRNA despite our findings of a CD2 7(-) cell accumulation within the synovial population of CD4 lymphocyt es. These are the first data to demonstrate that expression of the IL- 5 gene in RA SF CD27(-) lymphocytes is down-regulated and that IL-5 di sregulation in RA cannot be ruled out.