In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice: dependence upon CD4(+) cells and human MHC class II.
Staphylococcal enterotoxin (SE) B and seven other staphylococcal superantigens (SAg), despite promoting vigorous Ig production in human peripheral blood mononuclear cell cultures, are exceedingly poor at eliciting Ig responses in cultures of spleen cells from C57BL/10J (B10) or C3H/HeJ mice. In contrast, SEB elicits Ig responses in cultures of spleen cells from human MHC class II-transgenic mice. Whereas i.p. administration of SEB (0.2-20 microg) to non-transgenic B10 mice elicits very weak in vivo Ig responses, identical treatment of CD4(+) cell-intact (but not CD4(+) cell-depleted) human MHC class II-transgenic mice elicits dramatic increases in both splenic Ig-secreting cells and serum Ig levels. Over a 2-week period, the SEB-induced in vivo Ig responses peak and then plateau or fall in association with a preferential increase in splenic CD8(+) cells. Nevertheless, in vivo depletion of CD8(+) cells has no sustained effect on SEB-driven Ig responses. Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune responses are highly CD4(+) cell dependent, are substantially CD8(+) cell independent and can be successfully investigated using human MHC class II-transgenic mice. This model system may be useful in investigating the polyclonally activating effects of microbial products (prototypic environmental insults) on the development of systemic autoimmunity.
Stohl
W
W
Division of Rheumatology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA.
Xu
D
D
Zang
S
S
Kim
K S
KS
Li
L
L
Hanson
J A
JA
Stohlman
S A
SA
David
C S
CS
Jacob
C O
CO
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D004768:Enterotoxins / Q000276:immunology; D019674:Genes, T-Cell Receptor beta; D006683:HLA-DQ Antigens / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
D000942:Antigens, Bacterial; D004768:Enterotoxins; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015802:HLA-DR2 Antigen; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C109168:T-cell receptor Vbeta 8.2; C031818:enterotoxin B, staphylococcal