Am. J. Respir. Crit. Care Med., Vol 149, No. 4, Apr 1994, 972-980.
Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions
B Sadat-Sowti, A Parrot, L Quint, C Mayaud, P Debre and B Autran
Laboratoire d'Immunologie Cellulaire et Tissulaire, CERVI, Group Pitie- Salpetriere, Paris, France.
We investigated the CD8+CD57+ alveolar cell functions and their
immunoregulatory role in lungs from HIV-seropositive patients with the
clinical presentation of lymphocytic alveolitis at different stages of
human immunodeficiency virus (HIV) disease. We previously reported, at
Stage IV of HIV infection, an expansion of CD8+CD57+ alveolar lymphocytes
mirroring the decline of local anti-HIV cytotoxic T- lymphocyte (CTL)
responses, and demonstrated that sorted CD8+CD57+ alveolar lymphocytes
inhibited the effector phase of these HIV-specific CTL. In the present
study, we show that the expansion of CD8+CD57+ alveolar T cells can also be
detected at stages II and III of HIV disease, although at a lower degree
than observed at Stage IV of HIV infection. When sorted, these CD8+CD57+
alveolar lymphocytes block effector killer cells such as allospecific CTL,
natural killer (NK), and lymphokine-activated killer (LAK) cells. The
mechanism of action of these inhibitory T-lymphocytes has been further
studied and we demonstrated that: (1) cell-to-cell contact between
inhibitor and killer is not required, (2) nonstimulated alveolar
CD8+CD57+lymphocytes but not CD57- lymphocytes spontaneously release a
solube inhibitor of cytolytic functions (ICF). This inhibitory activity of
alveolar CD8+CD57+ cells is mediated by a glycosylated protein which is
distinct from tumor necrosis factor-alpha (TNF alpha), TNF beta,
transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, interferon
alpha (IFN alpha), interferon gamma (IFN gamma), and prostaglandins. The
release of such an inhibitor of killer cell functions by CD8+CD57+
lymphocytes in the lungs, which are an important interface between the
sterile body and the antigen-laden environment, may play a role in the
local control of cell immunity.
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Copyright © 1994 American Thoracic Society
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