TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice.
In previous reports, we showed that tumor-derived TGF-beta induced overproduction of IL-10, and these suppressive cytokines caused macrophage suppression in EL4-bearing mice. Proliferation of T cells from EL-4, but not IL-2, whereas T cells from normal mice were responsive to IL-2. A balance between Th1- and Th2-type cytokine production in EL4-T in response to anti-CD3 Ab or phorbor myristate acetate plus A23187 shifted toward the Th2 dominant pattern. The prevention of TGF-beta and IL-10 activates in vivo by administration of anti-IL-10 Ab (anti-IL-10) or anti TGF-beta Ab (anti-TGF-beta) resulted in the reduction in EL4-T of both IL-4 dependent proliferation and Th2-dominant cytokine production induced by anti-CD-3 stimulation. In addition, the anti-TGF-beta treatment resulted in complete restoration in EL4-T of suppressed IL-2 responsiveness, IL-2R expression, and Th1-type cytokine production, whereas the anti-IL-10 treatment produced partial recovery. These results lead us to conclude that TGF-beta drives the shift in the Th1/Th2 balance toward Th2 via IL-10-mediated development of the Th2 responses and via inhibition of the Th1-type responses directly in EL4-bearing mice.
Maeda
H
H
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Shiraishi
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013945:Thymoma; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4