Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions.
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.
Sadat-Sowti
B
B
Laboratoire d'Immunologie Cellulaire et Tissulaire, CERVI, Group Pitié-Salpétrière, Paris, France.
Parrot
A
A
Quint
L
L
Mayaud
C
C
Debre
P
P
Autran
B
B
D017088:AIDS-Related Opportunistic Infections; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018959:CD57 Antigens; D016827:CD8 Antigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D018189:Immunomagnetic Separation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018959:CD57 Antigens; D016827:CD8 Antigens