Differentiation of naive CD4+ T cells towards T helper 2 cells is not impaired in rheumatoid arthritis patients.
An impaired differentiation of naive CD4+ T cells towards Th2 cells may contribute to the chronic tissue-destructive T-cell activity in rheumatoid arthritis (RA). The differentiation of naive CD4+ T cells into memory Th2 cells by IL-7 in comparison with that by IL-4 was studied in RA patients and in healthy controls. Naive CD4+ T cells from peripheral blood were differentiated by CD3/CD28 costimulation in the absence of or in the presence of IL-7 and/or IL-4. The production of IFN-gamma and IL-4 was measured by ELISA and by single-cell FACS analysis to indicate Th1 and Th2 cell activity. CD3/CD28 costimulation and IL-7 were early inducers of IL-4 production, but primarily stimulated IFN-gamma production. In contrast, in short-term cultures exogenously added IL-4 did not prime for IL-4 production but suppressed IL-7-induced IFN-gamma production. Upon long-term stimulation of naive CD4+ T cells, IFN-gamma production was differentially regulated by IL-7 and IL-4, but IL-4 production was increased by both IL-7 and IL-4. IL-7 and IL-4 additively induced polarization towards a Th2 phenotype. This susceptibility of naive CD4+ T cells to become Th2 cells upon culture with IL-7 and IL-4 was increased in RA patients compared with that in healthy controls. These findings demonstrate that, in RA patients, differentiation of naive CD4+ T cells towards a Th2 phenotype by CD3/CD28 costimulation, IL-7 and IL-4 is not impaired. The perpetuation of arthritogenic T-cell activity in RA therefore seems not to be the result of intrinsic defects of naive CD4+ T cells to develop towards suppressive memory Th2 cells.
van Roon
Joël A G
JA
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands. j.vanroon@azu.nl
Glaudemans
Catharina A F M
CA
Bijlsma
Johannes W J
JW
Lafeber
Floris P J G
FP
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D018106:CD28 Antigens; D017252:CD3 Complex; D015851:Interleukin-7; D015847:Interleukin-4