Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus.
In response to appropriate stimulation, T lymphocytes from systemic lupus erythematosus (SLE) patients exhibit increased and faster intracellular tyrosine phosphorylation and free calcium responses. We have explored whether the composition and dynamics of lipid rafts are responsible for the abnormal T cell responses in SLE. SLE T cells generate and possess higher amounts of ganglioside-containing lipid rafts and, unlike normal T cells, SLE T cell lipid rafts include FcRgamma and activated Syk kinase. IgM anti-CD3 Ab-mediated capping of TCR complexes occurs more rapidly in SLE T cells and concomitant with dramatic acceleration of actin polymerization kinetics. The significance of these findings is evident from the observation that cross-linking of lipid rafts evokes earlier and higher calcium responses in SLE T cells. Thus, we propose that alterations in the lipid raft signaling machinery represent an important mechanism that is responsible for the heightened and accelerated T cell responses in SLE.
Krishnan
Sandeep
S
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Nambiar
Madhusoodana P
MP
Warke
Vishal G
VG
Fisher
Carolyn U
CU
Mitchell
Jeanne
J
Delaney
Nancy
N
Tsokos
George C
GC
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005732:Gangliosides / Q000032:analysis; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry* / Q000276:immunology; D008875:Middle Aged; D011940:Receptor Aggregation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure*
D000199:Actins; D005732:Gangliosides; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG