Encephalitogenic Th1 cells are inhibited by Th2 cells with related peptide specificity: relative roles of interleukin (IL)-4 and IL-10.
Cytokines secreted by T-helper type 2 (Th2) cells inhibit the antigen-induced stimulation of type 1 (Th1) helper T cells. To study this form of regulation in an autoimmune disease model, the cytokines secreted by a Th2 clone specific for the encephalitogenic proteolipid protein (PLP) peptide 139-151 were tested for their ability to inhibit proliferation of an encephalitogenic Th1 clone specific for an epitope contained within the same peptide. Cytokines, produced by stimulation of the Th2 clone with CD3-specific monoclonal antibodies (mAbs), inhibited proliferation of the Th1 clone when stimulated by antigen and splenic antigen-presenting cells (APC). Inhibition was, however, not antigen-specific since cytokines released upon stimulation of an unrelated Th2 clone were also inhibitory. Inhibition was found to be caused by effects on either antigen presentation or co-stimulatory activity of the APC and not by direct effects on the Th1 cells. MAbs for the two major regulatory Th2 cytokines were used to identify the inhibitory component secreted by activated Th2 cells. Interleukin-10 (IL-10)-specific mAb abolished the inhibitory effect, while mAb specific for IL-4 had no effect on inhibition. The addition of recombinant IL-4 (rIL-4) and rIL-10 confirmed that inhibition of Th1 proliferation was due to secretion of IL-10 by the Th2 clone and its subsequent effects on APC. The studies described here demonstrate that PLP-specific Th2 cells which recognize peptide 139-151 inhibit encephalitogenic Th1 cells which respond to an epitope on the same peptide. This phenomenon may be important for local, antigen-specific regulation of inflammation in the central nervous system.
van der Veen
R C
RC
Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Stohlman
S A
SA
D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D016753:Interleukin-10; D015847:Interleukin-4