Absence of a prominent Th2 cytokine response in human tuberculosis

Depressed Th1 responses are a prominent feature of human tuberculosis, but an enhanced Th2 response has not been detected in peripheral blood T cells stimulated in vitro with Mycobacterium tuberculosis. In disease due to Mycobacterium leprae, Th2 cells predominate in tissue lesions of patients with extensive disease but are absent from peripheral blood. To determine if Th2 cells are present in tissue lesions of tuberculosis patients, we evaluated patterns of cytokine expression in lymph nodes from tuberculosis patients with or without human immunodeficiency virus infection and in controls without tuberculosis. Gamma interferon and interleukin-10 (IL-10) mRNA expression in tuberculosis patients with or without human immunodeficiency virus infection was high, whereas IL-4 expression in the same patients was low. Immunolabeling studies showed that macrophage production of IL-12 was increased in lymph nodes from tuberculosis patients, that gamma interferon was produced by T cells, and that IL-10 was produced by macrophages rather than Th2 cells. These results indicate that Th2 responses are not enhanced either systemically or at the site of disease in human tuberculosis.

[1]  J. Abrams,et al.  Cytokine production at the site of disease in human tuberculosis , 1993, Infection and immunity.

[2]  J. Abrams,et al.  Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. , 1993, Journal of immunology.

[3]  M. de Carli,et al.  Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. , 1992, Journal of immunology.

[4]  S. Kaufmann,et al.  Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha , 1995, The Journal of experimental medicine.

[5]  C. Hsieh,et al.  Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. , 1993, Science.

[6]  J. Abrams,et al.  T-cell cytokine responses in human infection with Mycobacterium tuberculosis , 1995, Infection and immunity.

[7]  A. Sher,et al.  Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Mitchell,et al.  Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis. , 1994, American journal of respiratory and critical care medicine.

[9]  M. Gately,et al.  Interleukin 12 at the site of disease in tuberculosis. , 1994, The Journal of clinical investigation.

[10]  W. Stead.  Management of Health Care Workers after Inadvertent Exposure to Tuberculosis: A Guide for the Use of Preventive Therapy , 1995, Annals of Internal Medicine.

[11]  Giorgio,et al.  Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells , 1992, The Journal of experimental medicine.

[12]  D. Snider,et al.  Tuberculosis in patients with human immunodeficiency virus infection. , 1991, The New England journal of medicine.

[13]  R. Schaub,et al.  Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response , 1993, The Journal of experimental medicine.

[14]  H. Shiratsuchi,et al.  Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions. , 1995, Journal of immunology.

[15]  J. Flynn,et al.  IL-12 increases resistance of BALB/c mice to Mycobacterium tuberculosis infection. , 1995, Journal of immunology.

[16]  J. Abrams,et al.  Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. , 1992, Journal of immunology.

[17]  Alan D. Roberts,et al.  The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. , 1995, Immunology.

[18]  M. Piccinni,et al.  Interleukin 12 Induces Stable Priming for Interferon 3' (IFN-3") Production During Differentiation of Human T Helper (Th) Cells and Transient IFN-3' Production in Established Th2 Cell Clones By Roberto Manetti,* Franca Gerosa,~ Maria Grazia Giudizi,* , 1994 .

[19]  R. Locksley,et al.  Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets , 1989, The Journal of experimental medicine.

[20]  Defining protective responses to pathogens: cytokine profiles in leprosy lesions. , 1991, Science.

[21]  G. Trinchieri,et al.  Interleukin 10 (IL-10) Inhibits Human Lymphocyte Interferon 3,-Production by Suppressing Natural Killer Cell Stimulatory Factor/IL-12 Synthesis in Accessory Cells By Annalisa D'Andrea, Miguel Aste-Amezaga, , 1993 .

[22]  G. Trinchieri,et al.  Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma- production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells , 1993, The Journal of experimental medicine.

[23]  T. Mosmann,et al.  IL-10 inhibits cytokine production by activated macrophages. , 1991, Journal of immunology.

[24]  S. Kaufmann,et al.  Early Interleukin 12 Production by Macrophages in Response to Mycobacterial Infection Depends on Interferon 3r and Tumor Necrosis Factor ol By Inge E. A. Flesch,* Jfirgen H. Hess,* Sui Huang,~ Michel Aguet,$ , 1995 .

[25]  R. Rerko,et al.  Recombinant interleukin 12 cures mice infected with Leishmania major , 1993, The Journal of experimental medicine.

[26]  J. Abrams,et al.  Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy. , 1993, Journal of immunology.

[27]  C G Figdor,et al.  Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes , 1991, The Journal of experimental medicine.

[28]  G. Trinchieri,et al.  Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones , 1994, The Journal of experimental medicine.

[29]  A. Waage,et al.  LOCAL PRODUCTION OF TUMOR NECROSIS FACTOR a , 1989 .

[30]  R. Coffman,et al.  Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens , 1988, The Journal of experimental medicine.

[31]  M. Troye-Blomberg,et al.  Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. , 1994, Immunology.

[32]  C. Pirmez,et al.  Cytokine patterns in the pathogenesis of human leishmaniasis. , 1993, The Journal of clinical investigation.

[33]  Dinakar,et al.  T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection. , 1994, The Journal of clinical investigation.

[34]  G. Trinchieri,et al.  Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells , 1993, The Journal of experimental medicine.

[35]  M. Gately,et al.  IL-12 regulates T helper type 1 cytokine responses in human infectious disease. , 1994, Journal of immunology.