The T cell antigen receptor CD3:CD4 molecular complex is diminished on the surface of pulmonary lymphocytes.
CD4, a 55-kd cell surface glycoprotein, binds to class II major histocompatibility complex (MHC) (Ia) antigens and functions as a coreceptor for the T cell antigen receptor (Ti alpha beta)-CD3 complex. We have observed that critical elements of the T cell antigen multireceptor complex, including Ti alpha beta, CD3, CD4, but not CD8, were diminished on CD45RO+ pulmonary T lymphocytes but not CD45RO+ peripheral blood T lymphocytes (PBL). Epitopes mapping from the first (D1) to the fourth (D4) extracytoplasmic Ig-like domains of CD4 were expressed to a lesser degree on pulmonary T cells than on PBL (P = 0.002). CD4 expression on pulmonary T cells did not increase after 72 hours of ex vivo culture in complete medium but was restored toward control levels by stimulation with phytohemagglutinin, anti-CD3, or interleukin-2. CD4 mRNA isolated from lung T cells and PBL co-migrated on Northern blots and the total levels of CD4 mRNA were comparable, suggesting that diminished CD4 expression by pulmonary T cells might reflect a posttranscriptional change. To determine whether CD4bright T cells convert with mitogen stimulation to CD4dim cells, PBLs were stimulated with immobilized anti-CD3, anti-CD4, or a molecularly engineered anti-CD3:CD4 bispecific monoclonal antibody and the ratio of the CD4:CD3 mean fluorescence staining intensities was calculated at days 3 and 13. The CD4:CD3 ratio decreased primarily for cells stimulated with anti-CD3:CD4, suggesting that co-ligation of CD3 and CD4 is required for the generation of CD4dim T cells. We conclude that diminished Ti alpha beta-CD3:CD4 expression is a characteristic of T cells in lung that is not shared by peripheral blood T cells in vivo, and speculate that this change reflects T cell activation in a millieu of limited interleukin-2 availability.
Department of Medicine, Massachusetts General Hospital, Boston 02114.
K
K
Marathias
C
C
Pinto
G
G
Rodberg
F
F
Preffer
J
J
Wong
R
R
Kradin
D018033:Antibodies, Bispecific / Q000276:immunology; D015152:Blotting, Northern; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D017493:Leukocyte Common Antigens; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D018033:Antibodies, Bispecific; D017252:CD3 Complex; D015704:CD4 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens