B7-1, but not CD28, is crucial for the maintenance of the CD4+ T cell responses in human leprosy.
We used human leprosy as a model to compare patterns of costimulatory molecule expression in respect to the clinical/immunologic spectrum of disease. We found that B7-1, B7-2, and CD28 transcripts dominated in tuberculoid leprosy patients, who have potent T cell responses to Mycobacterium leprae. In contrast, CTLA-4 was more strongly expressed in lesions from lepromatous patients, who manifest specific T cell anergy to the leprosy bacterium. T cell clones from tuberculoid lesions were CD4+CD28+ or CD4+CD28-, and T cell clones from lepromatous lesions were predominantly CD8+CD28-. The M. leprae-specific recall response of CD4+ T cell clones from tuberculoid lesions was blocked by anti-B7-1 mAb, but not by anti-B7-2 mAb or CTLA-Ig. However, anti-CD28 and anti-CTLA-4 mAbs did not block activation of clones from tuberculoid lesions, suggesting that B7-1 may utilize another costimulatory pathway. Peripheral blood T cell responses in the lepromatous form were strongly regulated by CD28 during T cell activation, in contrast to the tuberculoid form. Thus, B7-1 costimulation could play a role in maintaining a strong immune response to the pathogen.
Schlienger
K
K
Division of Dermatology, University of California-Los Angeles, School of Medicine 90095, USA.
Uyemura
K
K
Jullien
D
D
Sieling
P A
PA
Rea
T H
TH
Linsley
P S
PS
Modlin
R L
RL
D000069594:Abatacept; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000096:biosynthesis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D060908:CTLA-4 Antigen; D002999:Clone Cells; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D018796:Immunoconjugates; D015440:Leprosy, Lepromatous / Q000276:immunology* / Q000473:pathology; D015441:Leprosy, Tuberculoid / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009166:Mycobacterium leprae / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007106:Immune Sera; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept