CD8+ type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I- and class II-deficient mice.
Genetically engineered mice with a targeted disruption in the beta 2-microglobulin (beta 2-m) gene or the H2-I-A beta chain (A beta) which lack functional CD8+ or CD4+ T cells, respectively, were used to assess the role of T cell subsets in Brucella abortus infection. Murine brucellosis was markedly exacerbated in beta 2-m-deficient mice (beta 2-m-/-) compared to A beta mutant (A beta-/-) or C57BL/6 mice, strongly indicating that optimal resistance to B. abortus requires CD8+ T cells. Splenocytes from Brucella-primed beta 2-m-/-, A beta-/- and C57BL/6 mice exhibited a type 1 cytokine profile marked by elevated IFN-gamma mRNA expression and protein production, and basal levels of IL-2 and IL-4 transcripts. B. abortus did not induce secretion of TGF-beta 1, but substantial IL-10 activity was detected in spleen cell supernatants from all mouse strains studied. CD8+ T cells from A beta-/- and C57BL/6 mice displayed a CD44hi CD45RBlo phenotype and a type 1 cytokine transcription profile featuring high levels of IFN-gamma mRNA. Additionally, we have shown the ability of C57BL/6 CD8+ CTL to kill Brucella-infected macrophages. This study illustrates the predominant role of MHC class I-restricted T cells in controlling B. abortus infection.
Oliveira
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Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706, USA.
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D000818:Animals; D002003:Brucella abortus; D002006:Brucellosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013154:Spleen / Q000276:immunology* / Q000382:microbiology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1