Elevated production of interferon-gamma and interleukin 4 by mature T cells from autoimmune lpr mice correlates with Pgp-1 (CD44) expression.
The cell surface glycoprotein, Pgp-1 (CD44), has been shown to be a marker of murine memory T lymphocytes. When activated, Pgp-1hi memory T cells produce strikingly higher amounts of interferon-gamma (IFN-gamma) than naive Pgp-1lo T cells, yet both subsets make similar levels of interleukin (IL)2. Whereas Pgp-1hi cells represent only 20%-25% of peripheral T cells from most strains, this marker is expressed by the vast majority (greater than 90%) of T cells from autoimmune MRL mice homozygous for the lymphoproliferation (lpr) gene. The massive lymphadenopathy that develops in lpr/lpr mice is composed of both non-mature (CD4-CD8-) T cells as well as a greatly expanded number (up to 300-fold) of mature (CD4+CD8-,CD4-CD8+) T cells. Paralleling the expression of high levels of Pgp-1, we find that compared to normal mouse T cells, the lpr mature T lymphocyte subsets are also very high producers on a per cell basis of IFN-gamma and, for the CD4+ subset, IL 4. Increased concentrations of IFN-gamma and IL 4 produced by large numbers of lpr Pgp-1hi mature T cells could contribute to the autoimmune syndrome in MRL lpr/lpr mice through the effects of these cytokines on augmenting MHC class II expression and production of certain classes of antibodies.
Budd
R C
RC
Rheumatology and Clinical Immunology Unit, University of Vermont College of Medicine, Burlington 05405.
Schumacher
J H
JH
Winslow
G
G
Mosmann
T R
TR
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D016201:Receptors, Lymphocyte Homing; D015847:Interleukin-4; D007371:Interferon-gamma