Involvement of HLA-DR+ large granular lymphocytes in the induction of tumor necrosis factor by Mycobacterium avium-intracellulare complex.
This study shows that normal human large granular lymphocytes (LGL) secrete tumor necrosis factor (TNF) in response to Mycobacterium avium-intracellulare complex (MAI). Percoll density gradient fractionation of peripheral mononuclear cells showed TNF activity in the fractions corresponding to LGL and not T cells, even when 5% monocytes were added to the T lymphocytes for accessory function. TNF release was not abrogated by treatment of the crude LGL preparations with anti-Leu M3, -CD4, and -CD8 antibodies (Ab) plus complement (C), but was abrogated by anti-CD16 and -CD2 Ab, as expected. Interestingly, anti-HLA-DR monoclonal antibody (mAb) treatment significantly diminished TNF activity from LGL, but maintained natural killer (NK) cell function unmodified as opposed to CD2+ and CD16+ cell depletion. Panning studies demonstrated that TNF secretion upon MAI stimulation resided only in the HLA-DR+ LGL and not the DR- LGL population. These results indicate that normal fresh HLA-DR+ LGL, as well as monocytes, are also responsible for rapid TNF secretion during early MAI infection. These DR+ cells appear to be distinct from those expressing NK function.
Michelini-Norris
M B
MB
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612.
Blanchard
D K
DK
Friedman
H
H
Djeu
J Y
JY
D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018801:CD2 Antigens; D002469:Cell Separation; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D006684:HLA-DR Antigens; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha