scholarly journals Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses

Immunology ◽  
1999 ◽  
Vol 97 (4) ◽  
pp. 588-594 ◽  
Author(s):  
Mountford ◽  
Coulson ◽  
Cheever ◽  
A. Sher ◽  
R. A. Wilson ◽  
...  
2003 ◽  
Vol 71 (12) ◽  
pp. 7215-7218 ◽  
Author(s):  
Andrea Debus ◽  
Joachim Gläsner ◽  
Martin Röllinghoff ◽  
André Gessner

ABSTRACT Myeloid differentiation protein 88 (MyD88) is a general adaptor for the signaling cascade through receptors of the Toll/IL-1R family. When infected with Leishmania major parasites, MyD88-deficient mice displayed a dramatically enhanced parasite burden in their tissues similar to that found in susceptible BALB/c mice. In contrast, MyD88 knockout mice did not develop ulcerating lesions despite a lack of interleukin-12 (IL-12) production and a predominant T helper 2 cell response. Blockade of IL-4 produced early (day 1) after infection restored a protective T helper 1 response in MyD88 knockout mice.


1994 ◽  
Vol 179 (4) ◽  
pp. 1273-1283 ◽  
Author(s):  
R Manetti ◽  
F Gerosa ◽  
M G Giudizi ◽  
R Biagiotti ◽  
P Parronchi ◽  
...  

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.


Immunology ◽  
2000 ◽  
Vol 99 (1) ◽  
pp. 109-112 ◽  
Author(s):  
K. M. Gillespie ◽  
C.-C. Szeto ◽  
V. M. Betin ◽  
P. W. Mathieson

1988 ◽  
Vol 168 (2) ◽  
pp. 543-558 ◽  
Author(s):  
R Fernandez-Botran ◽  
V M Sanders ◽  
T R Mosmann ◽  
E S Vitetta

Murine Th1 and Th2 subsets differ not only in the lymphokines they produce, but also functionally. It is not clear what factors influence the preferential activation of one subset versus the other and what regulatory interactions exist between them. The purpose of this study was to examine the effect of lymphokines produced by clones of Th1 cells (IL-2 and IFN-gamma), Th2 cells (IL-4), and APC (IL-1) on the proliferative response of Th1 and Th2 cells after antigenic stimulation. Activation of both types of clones in the presence of antigen and APC resulted in the acquisition of responsiveness to the proliferative effects of both IL-2 and IL-4, although Th2 cells were more responsive to IL-4 than Th1 cells. Responsiveness of Th1 and Th2 cells to both lymphokines decreased with time after initial antigenic activation; Th1 cells lost their responsiveness to IL-4 more rapidly and to IL-2 more slowly than Th2 cells. IFN-gamma partially inhibited the IL-2 and IL-4-mediated proliferation of Th2, but not Th1 cells. Although the presence of IL-1 was not required for the response of Th1 or Th2 cells to IL-4, its presence resulted in a synergistic effect with IL-2 or IL-4 in Th2 but not in Th1 cells. Both subsets responded to a mixture of IL-2 and IL-4 in synergistic fashion. Delayed addition and wash-out experiments indicated that both IL-2 and IL-4 had to be present simultaneously in order for synergy to occur. These results suggest that Th cell subsets might regulate each other via the lymphokines that they secrete and that the pathways of IL-2 and IL-4 mediated proliferation are interrelated.


2005 ◽  
Vol 67 (5) ◽  
pp. 521-524 ◽  
Author(s):  
Kazunori IKE ◽  
Yuko UCHIDA ◽  
Tomohiko NAKAMURA ◽  
Soichi IMAI

Immunology ◽  
2003 ◽  
Vol 108 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Kevin G. J. Pollock ◽  
Margaret Conacher ◽  
Xiao-Qing Wei ◽  
James Alexander ◽  
James M. Brewer

Sari Pediatri ◽  
2016 ◽  
Vol 10 (3) ◽  
pp. 207
Author(s):  
Yolanda Olivia Palandeng ◽  
Diana Devi Takumansang Sondakh

Latar belakang. Prevalensi asma makin meningkat, diduga berkaitan dengan kejadian infeksi pada anak yang menurun sehingga menyebabkan pergeseran keseimbangan antara limfosit T helper 1 (Th1) dan T helper 2 (Th2) ke arah predominan Th2. Infeksi mikobakterium dan vaksinasi BCG dapat meningkatkan respon imun Th1 (interferon gamma (IFN-γ)) dan menekan Th2.Tujuan. Mengetahui pengaruh vaksinasi BCG terhadap kadar IFN-γ serum pasien asma ekstrinsik atopi anak setelah vaksinasi BCG satu kali.Metode. Penelitian kuasi-eksperimental pretest posttest control group design pada anak asma atopi. Pengacakan perlakuan dilakukan terhadap subjek ke dalam kelompok BCG dan plasebo. Sebelum dan 8 minggu sesudah perlakuan diukur kadar IFN-γ serum.Hasil. Kadar IFN-γ serum tidak meningkat sesudah vaksinasi BCG (median 1,580 dan 0,780 pg/ml, p= 0,326) dan plasebo (median 1,255 dan 0,670 pg/ml, p= 0,079). Selisih kadar IFN-γ serum kelompok BCG dan plasebo tidak berbeda bermakna (median 0,020 dan -0,420 pg/ml, p= 0,449).Kesimpulan. Kadar IFN-γ serum pasien asma ekstrinsik atopi anak tidak meningkat setelah vaksinasi BCG 1 kali.


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