scholarly journals Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

1996 ◽  
Vol 9 (4) ◽  
pp. 532-562 ◽  
Author(s):  
D R Lucey ◽  
M Clerici ◽  
G M Shearer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gamma Interferon ◽  
Human Diseases ◽  
Delayed Type Hypersensitivity ◽  
Type 2 Cytokines ◽  
Th1 And Th2

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

scholarly journals Differential Cytokine Pattern in the Spleens and Livers of BALB/c Mice Infected with Penicillium marneffei: Protective Role of Gamma Interferon

2003 ◽  
Vol 71 (1) ◽  
pp. 465-473 ◽  
Author(s):  
Francesca Sisto ◽  
Annarita Miluzio ◽  
Orazio Leopardi ◽  
Maurizio Mirra ◽  
Johan R. Boelaert ◽  
...  
Keyword(s):  
Immune Response ◽  
Gamma Interferon ◽  
Penicillium Marneffei ◽  
Yeast Cells ◽  
Interleukin 12 ◽  
Type 2 Cytokines ◽  
Ifn Γ

ABSTRACT Penicillium marneffei is an intracellular opportunistic fungus causing invasive mycosis in AIDS patients. T cells and macrophages are important for protection in vivo. However, the role of T-cell cytokines in the immune response against P. marneffei is still unknown. We studied by semiquantitative reverse transcription-PCR and biological assays the patterns of expression of Th1 and Th2 cytokines in the organs of wild-type (wt) and gamma interferon (IFN-γ) knockout (GKO) mice infected intravenously with P. marneffei conidia. At 3 × 105 conidia/mouse, a self-limiting infection developed in wt BALB/c mice, whereas all GKO mice died at day 18 postinoculation. Splenic and hepatic granulomas were present in wt mice, whereas disorganized masses of macrophages and yeast cells were detected in GKO mice. The infection resolved faster in the spleens than in the livers of wt mice and was associated with the local expression of type 1 cytokines (high levels of interleukin-12 [IL-12] and IFN-γ) but not type 2 cytokines (low levels of IL-4 and IL-10). Conversely, both type 1 and type 2 cytokines were detected in the livers of wt animals. Disregulation of the cytokine profile was seen in the spleens but not in the livers of GKO mice. The inducible nitric oxide synthase mRNA level was low and the TNF-α level was high in both spleens and livers of GKO mice compared to wt mice. These data suggest that the polarization of a protective type 1 immune response against P. marneffei is regulated at the level of individual organs and that the absence of IFN-γ is crucial for the activation of fungicidal macrophages and the development of granulomas.

Age-dependent modifications of Type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans

2006 ◽  
Vol 127 (6) ◽  
pp. 560-566 ◽  
Author(s):  
S. Alberti ◽  
E. Cevenini ◽  
R. Ostan ◽  
M. Capri ◽  
S. Salvioli ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Type 2 Cytokines ◽  
Age Dependent ◽  
Memory Cd4 T Cells

Peyer's patch CD8+ memory T cells secrete T helper type 1 and type 2 cytokines and provide help for immunoglobulin secretion

1994 ◽  
Vol 24 (12) ◽  
pp. 3087-3092 ◽  
Author(s):  
Anand S. Lagoo ◽  
John H. Eldridge ◽  
Sandhya Lagoo-Deenadaylan ◽  
C. Allen Black ◽  
Ben U. Ridwan ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
T Helper ◽  
Peyer's Patch ◽  
Immunoglobulin Secretion ◽  
Type 2 Cytokines ◽  
Cd8 Memory T Cells ◽  
Helper Type

scholarly journals Dysregulated Synthesis of Intracellular Type 1 and Type 2 Cytokines by T Cells of Patients with Cutaneous T-Cell Lymphoma

1999 ◽  
Vol 6 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Bang-Ning Lee ◽  
Madeleine Duvic ◽  
Chih-Kwang Tang ◽  
Carlos Bueso-Ramos ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Study Groups ◽  
Cutaneous T Cell Lymphoma ◽  
Healthy Donors ◽  
Type 2 Cytokines ◽  
Ifn Γ

ABSTRACT Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-γ]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7+, in patients with SS, it was CD7−. Although the number of IL-4+CD4+ T cells was low for all study groups, there was a significantly higher number of IL-4+ CD8+ T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-γ-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-γ-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-γ may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.

scholarly journals Correction: Human CD141+ Dendritic Cells Induce CD4+ T Cells To Produce Type 2 Cytokines

2014 ◽  
Vol 193 (12) ◽  
pp. 6210-6210 ◽  
Author(s):  
Chun I. Yu ◽  
Christian Becker ◽  
Patrick Metang ◽  
Florentina Marches ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Type 2 Cytokines

scholarly journals Interleukin-10- and Transforming Growth Factor β-Independent Regulation of CD8+T Cells Expressing Type 1 and Type 2 Cytokines in Human Lymphatic Filariasis

2014 ◽  
Vol 21 (12) ◽  
pp. 1620-1627 ◽  
Author(s):  
Rajamanickam Anuradha ◽  
Parakkal Jovvian George ◽  
Paul Kumaran ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Lymphatic Filariasis ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β ◽  
Necrosis Factor Alpha ◽  
Type 2 Cytokines

ABSTRACTLymphatic filariasis is known to be associated with diminished CD4+Th1 and elevated CD4+Th2 responses to parasite-specific antigens. The roles of cytokine-expressing CD8+T cells in immune responses to filarial infections are not well defined. To study the roles of CD8+T cells expressing type 1, type 2, and type 17 cytokines in filarial infections, we examined the frequencies of these cells in clinically asymptomatic, patently infected (INF) individuals, directlyex vivoand in response to parasite or nonparasite antigens; these frequencies were compared with the results for individuals with filarial lymphedema (i.e., clinical pathology [CP]) and those without active infection or pathology (i.e., endemic normal [EN]). INF individuals exhibited significant decreases in the frequencies of CD8+T cells expressing tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-22 (IL-22) at baseline and/or in response to filarial antigens, compared with CP and EN individuals. In contrast, the same individuals exhibited significant increases in the frequencies of CD8+T cells expressing IL-4, IL-5, IL-9, IL-13, and IL-21, compared with CP and/or EN individuals. Curative treatment resulted in significantly increased frequencies of CD8+T cells expressing IL-2 and significantly decreased frequencies of CD8+T cells expressing type 2 cytokines. Finally, the regulation of these responses appears to be independent of IL-10 and transforming growth factor β (TGF-β), since blockade of IL-10 or TGF-β signaling did not significantly alter the frequencies of type 1 or type 2 cytokine-expressing CD8+T cells. Our findings suggest that alterations in the frequencies of cytokine-expressing CD8+T cells are characteristic features of lymphatic filarial infections.

scholarly journals The Virus-Encoded Chemokine vMIP-II Inhibits Virus-Induced Tc1-Driven Inflammation

2003 ◽  
Vol 77 (13) ◽  
pp. 7393-7400 ◽  
Author(s):  
Morten Lindow ◽  
Anneline Nansen ◽  
Christina Bartholdy ◽  
Annette Stryhn ◽  
Nils J. V. Hansen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Human Herpesvirus ◽  
Delayed Type Hypersensitivity ◽  
Intravenous Route ◽  
Antiviral Immune Response

ABSTRACT The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell-mediated inflammation. This was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. Mice were infected in the footpad, and the induced CD8+ T-cell-dependent inflammation was evaluated in mice subjected to treatment with vMIP-II. We found that inflammation was markedly inhibited in mice treated during the efferent phase of the antiviral immune response. In vitro studies revealed that vMIP-II inhibited chemokine-induced migration of activated CD8+ T cells, but not T-cell-target cell contact, granule exocytosis, or cytokine release. Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were injected directly into the test site. In contrast to the marked inhibition of the effector phase, the presence of vMIP-II during the afferent phase of the immune response did not result in significant suppression of virus-induced inflammation. Taken together, these results indicate that chemokine-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation.

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