Human CTLA-4 is expressed in situ on T lymphocytes in germinal centers, in cutaneous graft-versus-host disease, and in Hodgkin's disease.
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a molecule expressed on in vitro activated T cells. CTLA-4 shares important sequence homology with CD28 and binds to the same ligands, CD80 (B7-1) and CD86 (B7-2). CTLA-4 probably functions as a negative regulator of T lymphocyte activation in the mouse, although this remains to be proven for human T lymphocytes. We have developed new monoclonal antibodies against human CTLA-4 and have investigated the in situ expression of CTLA-4 in a wide variety of normal and pathological human tissues expressing CD80 and CD86. As revealed in this study, CTLA-4 is expressed on thymocytes in thymic medulla, on a subset of CD4+ T lymphocytes in germinal centers of follicular hyperplasia, on T cells, mainly CD8+, infiltrating skin affected by graft-versus-host disease, and on T cells, mainly CD4+, infiltrating Hodgkin's disease lesions. In immunoelectron microscopy, CTLA-4 was found on the plasma membrane as well as in the hyaloplasm and cytoplasmic vesicles, in agreement with its pattern of expression on in vitro activated T cells. Interestingly, no or at most scarce expression of CTLA-4 was found in granulomatous lymph nodes, T-cell-mediated inflammatory diseases, or non-Hodgkin's lymphomas, regardless of their expression of CD80 or CD86. Thus, expression of CTLA-4 appears to be induced in selective pathological conditions in vivo. The pathways leading to selective induction of CTLA-4 and its role in the pathophysiology of these conditions need to be further investigated.
Vandenborre
K
K
Laboratory for Experimental Hematology, University of Leuven, Belgium.
Delabie
J
J
Boogaerts
M A
MA
De Vos
R
R
Lorré
K
K
De Wolf-Peeters
C
C
Vandenberghe
P
P
D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003106:Colon / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D018858:Germinal Center / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D012871:Skin Diseases / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept