Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies.

TLDR

The study discusses how the distinct cytokine expression patterns of Th1 and Th2 clones inform the behavior of normal T cells. The authors evaluated 19 T cell clones by mRNA hybridization of 11 cytokine genes and developed monoclonal‑antibody–based bioassays and an ELISA to measure IL‑2, IL‑3, IL‑4, and IFN‑γ. Th1 clones uniquely express IL‑2, IFN‑γ, and lymphotoxin, whereas Th2 clones uniquely express IL‑4, IL‑5, and P600, with additional preferential expression of GM‑CSF, TNF, TY5 by Th1 and preproenkephalin by Th2, while IL‑3 is shared, and protein secretion correlates with mRNA levels.

Abstract

Lymphokine synthesis patterns of a panel of 19 T cell clones have been evaluated, using mRNA hybridization methods to examine 11 different mRNAs induced by Con A. The two types of CD4+ Th cell clone described previously were clearly distinguished by this procedure, and the differences between the two types have now been extended to six induced products. With minor exceptions, only Th1 clones synthesized mRNA for IL-2, IFN-gamma, and lymphotoxin, and only Th2 clones synthesized mRNA for IL-4, IL-5, and another induced gene, P600. Four more induced products were expressed preferentially but not uniquely by one or another type of clone: mRNAs for GM-CSF, TNF, and another induced, secreted product (TY5) were produced in larger amounts by Th1 clones, whereas preproenkephalin was preferentially expressed by Th2 clones. IL-3 was produced in similar amounts by both types of clone. mAbs were used to establish three bioassays that were functionally monospecific for IL-2, IL-3, and IL-4, and a new anti-IFN gamma mAb, XMG1.2, was used to establish an ELISA for IFN-gamma. These four assays were used to show that secreted protein and mRNA levels correlated well for all cell lines. The implications of these findings for normal T cells are discussed.