In vivo expression pattern of MICA and MICB and its relevance to auto-immunity and cancer.
Non-conventional MHC class I MIC molecules interact not with the TCR, but with NKG2D, a C-type lectin activatory receptor present on most NK, gammadelta and CD8(+) alphabeta T cells. While this interaction is critical in triggering/calibrating the cytotoxic activity of these cells, the actual extent of its in vivo involvement, in man, in infection, cancer or autoimmunity, needs further assessment. The latter has gained momentum along with the reported expansion of peripheral CD4(+)CD28(-)NKG2D(+) T cells in rheumatoid arthritis (RA). We first initiated to extend this report to a larger cohort of not only RA patients, but also those affected by systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). In RA and SS, this initial observation was further tested in target tissues: the joint and the salivary glands, respectively. In conclusion and despite occasional and indiscriminate expansion of the previously incriminated T cell subpopulation, no correlation could be observed between the CD4(+)CD28(-)NKG2D(+) and auto-immunity. Moreover, in situ, the presence of NKG2D matched that of CD8(+), but not that of CD4(+) T cells. In parallel, a total body tissue scan of both MICA and MICB transcription clearly shows that despite original presumptions, and with the exception of the central nervous system, both genes are widely transcribed and therefore possibly translated and membrane-bound. Extending this analysis to a number of human tumors did not reveal a coherent pattern of expression vs. normal tissues. Collectively these data question previous assumptions, correlating a tissue-specific expression/induction of MIC in relevance to auto-immune or tumor processes.
Schrambach
Stéphanie
S
Laboratoire Central d'Immunologie, Pôle de Biologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Immunogénétique Moléculaire Humaine, Centre de Recherce d'Immunologie et d'Hématologie, Faculté de Médecine Strasbourg, France.
Ardizzone
Marc
M
Leymarie
Vincent
V
Sibilia
Jean
J
Bahram
Seiamak
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D055815:Young Adult
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger