TY - JOUR
T1 - Differential regulation of T helper phenotype development by interleukins 4 and 10 in an αβ T-cell-receptor transgenic system
AU - Hsieh, C. S.
AU - Heimberger, A. B.
AU - Gold, J. S.
AU - O'Garra, A.
AU - Murphy, K. M.
PY - 1992
Y1 - 1992
N2 - To address the mechanisms controlling T helper (T(h)) phenotype development, we used DO10, a transgenic mouse line that expresses the αβ T- cell receptor from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting cells (APCs). We have examined the role of cytokines and APCs in the regulation of T(h) phenotype development. Interleukin 4 (IL-4) directs development toward the T(h2) phenotype, stimulating IL-4 and silencing IL-2 and interferon γ production in developing T cells. Splenic APCs direct development toward the T(h1) phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody. The splenic APCs mediating these effects are probably macrophages or dendritic cells and not B cells, since IL-10 is incapable of affecting T(h) phenotype development when the B-cell hybridoma TA3 is used as the APC. These results suggest that early regulation of IL-4 and IL-10 in a developing immune response and the identity of the initiating APCs are critical in determining the T(h) phenotype of the developing T cells.
AB - To address the mechanisms controlling T helper (T(h)) phenotype development, we used DO10, a transgenic mouse line that expresses the αβ T- cell receptor from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting cells (APCs). We have examined the role of cytokines and APCs in the regulation of T(h) phenotype development. Interleukin 4 (IL-4) directs development toward the T(h2) phenotype, stimulating IL-4 and silencing IL-2 and interferon γ production in developing T cells. Splenic APCs direct development toward the T(h1) phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody. The splenic APCs mediating these effects are probably macrophages or dendritic cells and not B cells, since IL-10 is incapable of affecting T(h) phenotype development when the B-cell hybridoma TA3 is used as the APC. These results suggest that early regulation of IL-4 and IL-10 in a developing immune response and the identity of the initiating APCs are critical in determining the T(h) phenotype of the developing T cells.
UR - http://www.scopus.com/inward/record.url?scp=0026648380&partnerID=8YFLogxK
U2 - 10.1073/pnas.89.13.6065
DO - 10.1073/pnas.89.13.6065
M3 - Article
C2 - 1385868
AN - SCOPUS:0026648380
VL - 89
SP - 6065
EP - 6069
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 13
ER -