The role of human alveolar macrophages in the allogeneic and autologous mixed leucocyte reactions.
Human alveolar macrophages (AM) are deficient in their ability to promote antigen-stimulated lymphocyte proliferation when compared to in-vitro-aged blood derived macrophages (BM). The mechanisms behind the unique accessory cell function of human AM are unknown. The current paradigm for accessory cell function requires antigen presentation in the context of gene products of the HLA-DR locus of the major histocompatibility complex (Class II, DR antigens) and secretion of non-specific second signal (e.g. interleukin 1). While both AM and in-vitro-aged BM have limited ability to secrete interleukin 1 (IL-1), more than 90% of both cell types express DR antigens. However, only BM consistently promote antigen-stimulated lymphocyte proliferation. Addition of IL-1 does not restore accessory cell function of human AM for antigen stimulation. It is possible that DR antigen expression and/or function of AM may be more contributory for their accessory cell function. The mixed leucocyte reaction (MLR) and autologous mixed leucocyte reactions (AMLR) in which DR epitopes stimulate proliferation of allogeneic and autologous T cells, respectively, are useful in vitro assays for assessment of DR-restricted macrophage-lymphocyte interactions. In the current studies we demonstrate that AM are usually equivalent to autologous in-vitro-aged BM in their ability to stimulate an MLR, but are consistently deficient relative to such BM in their ability to stimulate an AMLR. Experiments in which the two cells were co-cultured indicate that AM-mediated suppression does not account for the limited ability of AM to stimulate an AMLR. The deficiency of AM to act as accessory cells for antigen-stimulated lymphocyte proliferation may relate to their relative inability to stimulate autoreactive T cells and be attributable to differences in DR antigen expression and/or function.
Ettensohn
D B
DB
Department of Medicine, Memorial Hospital of Rhode Island, Pawtucket 02860.
Duncan
P G
PG
Jankowski
M J
MJ
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology*; D008297:Male; D011650:Pulmonary Alveoli / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D006684:HLA-DR Antigens