CD49d overexpression and T cell autoimmunity.
D10.G4.1 (D10) cells, a murine conalbumin-reactive Th2 cell line, made to overexpress the beta(2) integrin LFA-1 by pharmacological manipulation or by transfection become autoreactive and are capable of inducing in vivo autoimmunity. However, whether this is specific to LFA-1 and whether overexpression of other T cell integrin molecules has the same effect are unknown. We examined the functional consequences of T cell CD49d (alpha(4) integrin) overexpression by transfecting murine CD49d cDNA into D10 cells. Similar to the LFA-1-transfected cells, the CD49d-overexpressing T cells are autoreactive and proliferate in response to APCs in an MHC class II-dependent manner in the absence of nominal Ag. Additionally, CD49d overexpression is associated with increased in vitro adhesion to endothelial cells and increased in vivo splenic homing. However, in contrast to LFA-1 overexpression, increased T cell CD49d expression is not associated with autoreactive cytotoxicity or the ability to induce in vivo autoimmunity. In addition to the novel observation that CD49d overexpression is sufficient to induce T cell autoreactivity, our results also support the hypothesis that the ability to induce in vivo autoimmunity is related to T cell cytotoxicity and not to T cell proliferation function in the D10 murine adoptive transfer model of autoimmunity.
Mo
Ru-Ran
RR
Divisions of Geriatric Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Eisenbraun
Julie K
JK
Sonstein
Joanne
J
Craig
Ronald A
RA
Curtis
Jeffrey L
JL
Stoolman
Lloyd M
LM
Chen
Jun
J
Yung
Raymond L
RL
D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008806:Mice, Inbred AKR; D019463:Mice, Inbred MRL lpr; D010766:Phosphorylation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014443:Tyrosine / Q000378:metabolism
D000974:Antibodies, Antinuclear; D039441:Integrin alpha4; D014443:Tyrosine