MACROPHAGES INDUCE CELLULAR IMMUNITY BY ACTIVATING TH1 CELL RESPONSES AND SUPPRESSING TH2 CELL RESPONSES

作者: Hans Dooms , Johan Grooten , Walter Fiers , Pieter Rottiers , Marjory Desmedt

DOI:

关键词: Cellular differentiationAntigenAntigen-presenting cellCytokine secretionImmune toleranceImmune systemImmunologyCellular immunityHumoral immunityBiologyCell biology

摘要: Differentiation of naive CD4+ T cells (Th0) into Th1 or Th2 determines whether antigen will raise a cellular humoral immune response. The maturation pathway chosen by the Th0 cell is often decisive for outcome disease and depends among others on (co-)stimulatory attributes APC nature abundance cytokines provided microenvironment. In this study, we used macrophages, loaded ex vivo with antigen, inciting activation differentiation in vivo. macrophages were derived from clonal, immortalized population that both functionally phenotypically expressed features characteristic mature macrophages. Injection syngeneic mice IFN-gamma-treated, Ag-loaded induced primary response, indicated occurrence proliferative response vitro after restimulation splenocytes Ag. Analysis accompanying cytokine secretion revealed high numbers IFN-gamma-producing only few IL-4-secreting cells. This dominance had functional implications, reflected titer cell-dependent IgG2 Abs absence IgG1, immunity. Moreover, administration to an ongoing Th1/Th2 resulted complete suppression IgG1 production, whereas levels remained unaffected. These results demonstrate exert activity organism, strongly skew responses immunity, addition suppress already generated Th2-dependent thus characterizing these as Th1-oriented APC.

参考文章(43)
D T Umetsu, R H DeKruyff, R S Gieni, Antigen-driven but not lipopolysaccharide-driven IL-12 production in macrophages requires triggering of CD40. Journal of Immunology. ,vol. 158, pp. 359- 366 ,(1997)
P. Vandenabeele, V. Donckier, M.-L. Vanderhaeghen, Zoulikka Amraoui, D. Abramowicz, C. Bruyns, M. Goldman, C. Dubois, S. Florquin, IFN-gamma prevents Th2 cell-mediated pathology after neonatal injection of semiallogenic spleen cells in mice. Journal of Immunology. ,vol. 153, pp. 2361- 2368 ,(1994)
T F Gajewski, F W Fitch, M Pinnas, T Wong, Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. Journal of Immunology. ,vol. 146, pp. 1750- 1758 ,(1991)
A. O'garra, S. E. Macatonia, K. M. Murphy, P. Vieira, N. A. Hosken, M. Wysocka, Chyi-Song Hsieh, M. Litton, J. A. Culpepper, G. Trinchieri, Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. Journal of Immunology. ,vol. 154, pp. 5071- 5079 ,(1995)
M E Williams, P Caspar, A Sher, S L James, H K Sharma, I Oswald, O Pankewycz, Vaccination routes that fail to elicit protective immunity against Schistosoma mansoni induce the production of TGF-beta, which down-regulates macrophage antiparasitic activity. Journal of Immunology. ,vol. 154, pp. 4693- 4700 ,(1995)
P. S. Albert, D. E. Mcfarlin, D. Burnett, Seong-Hee Pak, M. K. Racke, B. Cannella, D. E. Scott, C. S. Raine, Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course. Journal of Immunology. ,vol. 154, pp. 450- 458 ,(1995)
CALOGERO CARUSO, GIUSEPPINA CANDORE, MARIA ASSUNTA MODICA, CESIRA TIZIANA BONANNO, GUIDO SIRECI, FRANCESCO DIELI, ALFREDO SALERNO, Major histocompatibility complex regulation of cytokine production Journal of Interferon and Cytokine Research. ,vol. 16, pp. 983- 988 ,(1996) , 10.1089/JIR.1996.16.983
M Yamamura, K Uyemura, R. Deans, K Weinberg, T. Rea, B. Bloom, R. Modlin, Defining protective responses to pathogens: cytokine profiles in leprosy lesions Science. ,vol. 254, pp. 277- 279 ,(1991) , 10.1126/SCIENCE.1925582