Spontaneous production of various cytokines except IL‐4 from CD4+ T cells in the affected organs of sarcoidosis patients

We investigated surface antigens and spontaneous cytokine production of T cells from broncho‐alveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7‐1) and CD86 (B70/B7‐2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty‐three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b‐ CD28‐ phenotypes. Most (61–90%) of these TCC spontaneously produced greater amounts of IL‐1a, IL‐10, tumour necrosis factor (TNF), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0·05). Interferon‐gamma (IFN‐γ), IL‐6, and IL‐2, but not IL‐4, were also produced by 40–48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.

[1]  C. Balch,et al.  Characterization of autologous tumor‐specific T‐helper 2 cells in tumor‐infiltrating lymphocytes from a patient with metastatic melanoma , 1994, International journal of cancer.

[2]  J. Gribben,et al.  Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. , 1993, Science.

[3]  L. Lanier,et al.  B70 antigen is a second ligand for CTLA-4 and CD28 , 1993, Nature.

[4]  S. Shichijo,et al.  A monoclonal antibody (H227) recognizing a new epitope of 4F2 molecular complex associated with T cell activation. , 1993, Cellular immunology.

[5]  M. Yokoyama,et al.  Tissue-specific distribution and age-dependent increase of human CD11b+ T cells. , 1993, Journal of immunology.

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

[7]  R. Coffman,et al.  Cytokine regulation of T-cell function: potential for therapeutic intervention. , 1993, Immunology today.

[8]  L. Lanier,et al.  Functional expression of B7/BB1 on activated T lymphocytes , 1993, The Journal of experimental medicine.

[9]  L. Lanier,et al.  CD28- T lymphocytes. Antigenic and functional properties. , 1993, Journal of immunology.

[10]  S. Durham,et al.  Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. , 1992, The New England journal of medicine.

[11]  L. Guilbert,et al.  A specific and reliable bioassay for the detection of femtomolar levels of human and murine tumor necrosis factors. , 1991, Journal of immunological methods.

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

[13]  P. Linsley,et al.  CTLA-4 is a second receptor for the B cell activation antigen B7 , 1991, The Journal of experimental medicine.

[14]  Roberta,et al.  Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. , 1991, The Journal of clinical investigation.

[15]  P. Linsley,et al.  Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation , 1991, The Journal of experimental medicine.

[16]  C. Morimoto,et al.  Effect of activation of protein kinase C on CD45 isoform expression and CD45 protein tyrosine phosphatase activity in T cells , 1990, European journal of immunology.

[17]  H. Jansen,et al.  Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. , 1990, Journal of immunology.

[18]  T. Mosmann,et al.  Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones , 1989, The Journal of experimental medicine.

[19]  C. Thompson,et al.  Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. , 1989, Science.

[20]  C. Balch,et al.  Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor , 1988, The Journal of experimental medicine.

[21]  R. Crystal,et al.  Spontaneous release of interleukin 2 by lung T lymphocytes in active pulmonary sarcoidosis is primarily from the Leu3+DR+ T cell subset. , 1986, The Journal of clinical investigation.

[22]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[23]  R. Crystal,et al.  Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. , 1985, The Journal of clinical investigation.

[24]  K. Rühle,et al.  Ia-like antigens on T-cells and their subpopulations in pulmonary sarcoidosis and in hypersensitivity pneumonitis. Analysis of bronchoalveolar and blood lymphocytes. , 1985, The American review of respiratory disease.

[25]  R. Crystal,et al.  Spontaneous release of interleukin-2 by lung T lymphocytes in active pulmonary sarcoidosis. , 1983, The New England journal of medicine.

[26]  S. Romagnani.  Lymphokine production by human T cells in disease states. , 1994, Annual review of immunology.