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Novel genetic regulation of T helper 1 (Th1)/Th2 cytokine production and encephalitogenicity in inbred mouse strains.

Conboy IM, DeKruyff RH, Tate KM, Cao ZA, Moore TA, Umetsu DT, Jones PP - J. Exp. Med. (1997)

Bottom Line: A splenic APC reduced IFN-gamma and TNF-alpha production by established Th1 MBP-specific Ak-restricted B10.BR TCL and by a Th1 KLH-specific, Ek-restricted B10.BR T cell clone.The nature of the downregulatory activity of B10.A APC on IFN-gamma and TNF-alpha production was explored. 2-hour supernatants from antigen-activated B10.A APC/TCL cultures or from B10.A APC activated by LPS had the same inhibitory effects on IFN-gamma and TNF-alpha production by B10.BR TCL.The downregulatory effects of B10.A APC are independent of TNF-alpha, IL-4, IL-10, IL-12p40, IFN-gamma, IL-13, TGF-beta, and PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Stanford University, California 94305-5020, USA.

ABSTRACT
Development of T helper cell (Th)1 or Th2 cytokine responses is essential for effector and regulatory functions of T helper cells. We have compared cytokine profiles of myelin basic protein (MBP) Ac1-16 peptide-specific T helper cells from inbred mouse strains expressing identical k haplotype-derived MHC class II molecules B10.A and B10.BR, B10.BR T cell lines (TCL) produced Th1 cytokines (including high levels of TNF-alpha) and induced experimental autoimmune encephalomyelitis after adoptive transfer. In contrast, B10.A TCL produced Th2 cytokines (including low levels of TNF-alpha) and were poorly encephalitogenic. The contributions of the genetic origin of the T cells and the APC were explored. Serial restimulations of the B10.BR TCL with B10.A or (B10.A x B10.BR) F1 splenic antigen presenting cells (APC) during the establishment of TCL markedly reduced both Th1 cytokine production and encephalitogenicity. In addition, a single restimulation with B10. A splenic APC reduced IFN-gamma and TNF-alpha production by established Th1 MBP-specific Ak-restricted B10.BR TCL and by a Th1 KLH-specific, Ek-restricted B10.BR T cell clone. These studies suggest that B10.A and B10.BR APC differ in their ability to stimulate IFN-gamma and TNF-alpha production by mature Th1 cells and also influence their Th1/Th2 commitment in vivo. The nature of the downregulatory activity of B10.A APC on IFN-gamma and TNF-alpha production was explored. 2-hour supernatants from antigen-activated B10.A APC/TCL cultures or from B10.A APC activated by LPS had the same inhibitory effects on IFN-gamma and TNF-alpha production by B10.BR TCL. The downregulatory effects of B10.A APC are independent of TNF-alpha, IL-4, IL-10, IL-12p40, IFN-gamma, IL-13, TGF-beta, and PGE2. Thus, genetic difference(s) between B10.A and B10.BR APC appear(s) to control the production or activity of a novel soluble cytokine regulatory factor that influences Th1/Th2 commitment and controls production of IFN-gamma and TNF-alpha by mature Th1 cells.

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Downregulatory effects of B10.A splenic APC on IFN-γ and  TNF-α production by a B10.BR-derived, KLH-specific, Ek-restricted T  cell clone. The BR E7 T cell clone was activated with KLH and either  B10.BR or B10.A splenic APC for two consecutive restimulations. Culture supernatants were harvested and assayed for TNF-α (A) and IFN-γ  (B) 24 h after stimulation. Data presented are means and standard deviations of triplicate wells for each sample (n = 3). Similar results were  ovserved in at least two additional experiments.
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Figure 7: Downregulatory effects of B10.A splenic APC on IFN-γ and TNF-α production by a B10.BR-derived, KLH-specific, Ek-restricted T cell clone. The BR E7 T cell clone was activated with KLH and either B10.BR or B10.A splenic APC for two consecutive restimulations. Culture supernatants were harvested and assayed for TNF-α (A) and IFN-γ (B) 24 h after stimulation. Data presented are means and standard deviations of triplicate wells for each sample (n = 3). Similar results were ovserved in at least two additional experiments.

Mentions: The cytokines produced by the B10.BRderived, KLH-specific, Ek-restricted Th1 clone BR E7 (62) were assayed after two consecutive restimulations with B10.BR or B10.A splenic APC. As shown in Fig. 7, presentation of KLH by B10.A APC results in the progressive reduction of IFN-γ and TNF-α levels produced by this Th1 clone. Thus, the B10.A APC-derived factor acts independently of the specificity of the Th1 and is able to downregulate IFN-γ and TNF-α production by a fully committed clonal Th1 population.


Novel genetic regulation of T helper 1 (Th1)/Th2 cytokine production and encephalitogenicity in inbred mouse strains.

Conboy IM, DeKruyff RH, Tate KM, Cao ZA, Moore TA, Umetsu DT, Jones PP - J. Exp. Med. (1997)

Downregulatory effects of B10.A splenic APC on IFN-γ and  TNF-α production by a B10.BR-derived, KLH-specific, Ek-restricted T  cell clone. The BR E7 T cell clone was activated with KLH and either  B10.BR or B10.A splenic APC for two consecutive restimulations. Culture supernatants were harvested and assayed for TNF-α (A) and IFN-γ  (B) 24 h after stimulation. Data presented are means and standard deviations of triplicate wells for each sample (n = 3). Similar results were  ovserved in at least two additional experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196024&req=5

Figure 7: Downregulatory effects of B10.A splenic APC on IFN-γ and TNF-α production by a B10.BR-derived, KLH-specific, Ek-restricted T cell clone. The BR E7 T cell clone was activated with KLH and either B10.BR or B10.A splenic APC for two consecutive restimulations. Culture supernatants were harvested and assayed for TNF-α (A) and IFN-γ (B) 24 h after stimulation. Data presented are means and standard deviations of triplicate wells for each sample (n = 3). Similar results were ovserved in at least two additional experiments.
Mentions: The cytokines produced by the B10.BRderived, KLH-specific, Ek-restricted Th1 clone BR E7 (62) were assayed after two consecutive restimulations with B10.BR or B10.A splenic APC. As shown in Fig. 7, presentation of KLH by B10.A APC results in the progressive reduction of IFN-γ and TNF-α levels produced by this Th1 clone. Thus, the B10.A APC-derived factor acts independently of the specificity of the Th1 and is able to downregulate IFN-γ and TNF-α production by a fully committed clonal Th1 population.

Bottom Line: A splenic APC reduced IFN-gamma and TNF-alpha production by established Th1 MBP-specific Ak-restricted B10.BR TCL and by a Th1 KLH-specific, Ek-restricted B10.BR T cell clone.The nature of the downregulatory activity of B10.A APC on IFN-gamma and TNF-alpha production was explored. 2-hour supernatants from antigen-activated B10.A APC/TCL cultures or from B10.A APC activated by LPS had the same inhibitory effects on IFN-gamma and TNF-alpha production by B10.BR TCL.The downregulatory effects of B10.A APC are independent of TNF-alpha, IL-4, IL-10, IL-12p40, IFN-gamma, IL-13, TGF-beta, and PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Stanford University, California 94305-5020, USA.

ABSTRACT
Development of T helper cell (Th)1 or Th2 cytokine responses is essential for effector and regulatory functions of T helper cells. We have compared cytokine profiles of myelin basic protein (MBP) Ac1-16 peptide-specific T helper cells from inbred mouse strains expressing identical k haplotype-derived MHC class II molecules B10.A and B10.BR, B10.BR T cell lines (TCL) produced Th1 cytokines (including high levels of TNF-alpha) and induced experimental autoimmune encephalomyelitis after adoptive transfer. In contrast, B10.A TCL produced Th2 cytokines (including low levels of TNF-alpha) and were poorly encephalitogenic. The contributions of the genetic origin of the T cells and the APC were explored. Serial restimulations of the B10.BR TCL with B10.A or (B10.A x B10.BR) F1 splenic antigen presenting cells (APC) during the establishment of TCL markedly reduced both Th1 cytokine production and encephalitogenicity. In addition, a single restimulation with B10. A splenic APC reduced IFN-gamma and TNF-alpha production by established Th1 MBP-specific Ak-restricted B10.BR TCL and by a Th1 KLH-specific, Ek-restricted B10.BR T cell clone. These studies suggest that B10.A and B10.BR APC differ in their ability to stimulate IFN-gamma and TNF-alpha production by mature Th1 cells and also influence their Th1/Th2 commitment in vivo. The nature of the downregulatory activity of B10.A APC on IFN-gamma and TNF-alpha production was explored. 2-hour supernatants from antigen-activated B10.A APC/TCL cultures or from B10.A APC activated by LPS had the same inhibitory effects on IFN-gamma and TNF-alpha production by B10.BR TCL. The downregulatory effects of B10.A APC are independent of TNF-alpha, IL-4, IL-10, IL-12p40, IFN-gamma, IL-13, TGF-beta, and PGE2. Thus, genetic difference(s) between B10.A and B10.BR APC appear(s) to control the production or activity of a novel soluble cytokine regulatory factor that influences Th1/Th2 commitment and controls production of IFN-gamma and TNF-alpha by mature Th1 cells.

Show MeSH
Related in: MedlinePlus