Type 1- and type 2-like lesional skin-derived Mycobacterium leprae-responsive T cell clones are characterized by coexpression of IFN-gamma/TNF-alpha and IL-4/IL-5/IL-13, respectively.

In an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN-gamma and IL-4 expression. To explore whether other cytokines are coproduced along with IFN-gamma and IL-4, we investigated the secretion of a panel of other cytokines (TNF-alpha, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-gamma/TNF-alpha (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-gamma/TNF-alpha, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.

[1]  S. Kaufmann,et al.  Impact of antigen-presenting cells on cytokine profiles of human Th clones established after stimulation with Mycobacterium tuberculosis antigens , 1995, Infection and immunity.

[2]  R. de Waal Malefyt,et al.  Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells. , 1995, International immunology.

[3]  M. de Carli,et al.  Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. , 1993, Journal of immunology.

[4]  T. J. Baker,et al.  Production, characterisation and use of monoclonal antibodies to human interleukin-5 in an enzyme-linked immunosorbent assay. , 1991, Journal of immunological methods.

[5]  L. Aarden,et al.  Human IL-13 production is negatively influenced by CD3 engagement. Enhancement of IL-13 production by cyclosporin A. , 1996, Journal of immunology.

[6]  D. Lockwood,et al.  Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions , 1995, Clinical and experimental immunology.

[7]  J. D. de Vries,et al.  Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. , 1994, Immunology today.

[8]  R. V. van Lier,et al.  Human atopen-specific types 1 and 2 T helper cell clones. , 1991, Journal of immunology.

[9]  H. Jansen,et al.  Comparison of diversity and function of house dust mite‐specific T lymphocyte clones from atopic and non‐atopic donors , 1990, European journal of immunology.

[10]  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.

[11]  A. Kelso Th1 and Th2 subsets: paradigms lost? , 1995, Immunology today.

[12]  J. Abrams,et al.  Patterns of cytokine production by mycobacterium-reactive human T-cell clones , 1993, Infection and immunity.

[13]  Kenneth M. Murphy,et al.  Functional diversity of helper T lymphocytes , 1996, Nature.

[14]  Ridley Ds,et al.  Classification of leprosy according to immunity. A five-group system. , 1966 .

[15]  R. Locksley,et al.  Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Romagnani Human TH1 and TH2 subsets: doubt no more. , 1991, Immunology today.

[17]  H. Schellekens,et al.  Monoclonal antibodies to human immune interferon and their use in a sensitive solid-phase ELISA. , 1985, Journal of immunological methods.

[18]  Elizabeth,et al.  Selection of a human T helper type 1-like T cell subset by mycobacteria , 1991, The Journal of experimental medicine.

[19]  L. Aarden,et al.  Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production , 1995, The Journal of experimental medicine.

[20]  H. Xiao,et al.  Clonal diversity of IL-4 and IL-13 expression in human allergen-specific T lymphocytes. , 1996, The Journal of allergy and clinical immunology.

[21]  R. Howe,et al.  Functional heterogeneity among CD4+ T-cell clones from blood and skin lesions of leprosy patients. Identification of T-cell clones distinct from Th0, Th1 and Th2. , 1995, Immunology.

[22]  R. de Waal Malefyt,et al.  IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. , 1992, Journal of immunology.

[23]  V. Ramesh,et al.  Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. , 1995, Immunology.

[24]  R. Coffman,et al.  Regulation of immunity to parasites by T cells and T cell-derived cytokines. , 1992, Annual review of immunology.

[25]  B. Bloom,et al.  Expression of adhesion molecules in leprosy lesions , 1991, Infection and immunity.

[26]  Ridley Ds Reactions in leprosy. , 1969 .

[27]  P. Lansdorp,et al.  Production of hybridoma growth factor by human monocytes , 1987, European journal of immunology.

[28]  J. Gerdes,et al.  IL‐10 secretion of allergen‐specific skin‐derived T cells correlates positively with that of the Th2 cytokines IL‐4 and IL‐5 * , 1994, Experimental dermatology.

[29]  C. Figdor,et al.  Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression , 1991, The Journal of experimental medicine.

[30]  K. Selmaj,et al.  Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro , 1988, Annals of neurology.

[31]  R. de Waal Malefyt,et al.  Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Piccinni,et al.  Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. D. de Vos,et al.  Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera. , 1991, Journal of immunological methods.

[34]  T. Ottenhoff,et al.  Analysis of cytokine production by Mycobacterium-reactive T cells. Failure to explain Mycobacterium leprae-specific nonresponsiveness of peripheral blood T cells from lepromatous leprosy patients. , 1993, Journal of immunology.

[35]  S. Akira,et al.  Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF) , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  R. Young,et al.  T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection. , 1997, Journal of immunology.

[37]  T. Mosmann,et al.  The expanding universe of T-cell subsets: Th1, Th2 and more. , 1996, Immunology today.

[38]  V. Kindler,et al.  The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection , 1989, Cell.

[39]  I. Rensink,et al.  Characterisation of monoclonal antibodies to human IL-4: application in an IL-4 ELISA and differential inhibition of IL-4 bioactivity on B cells and T cells. , 1993, European cytokine network.

[40]  P. Das,et al.  Reversal reaction in borderline leprosy is associated with a polarized shift to type 1-like Mycobacterium leprae T cell reactivity in lesional skin: a follow-up study. , 1997, Journal of immunology.

[41]  W. Jochum,et al.  T cells involved in psoriasis vulgaris belong to the Th1 subset. , 1994, The Journal of investigative dermatology.

[42]  J. Convit,et al.  Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. , 1991, Science.

[43]  A. Nakane,et al.  Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection , 1988, Infection and immunity.