International Immunology, Vol. 14, No. 7, pp. 801-812,
July 2002
© 2002 Japanese Society for Immunology
Staphylococcal enterotoxin B-induced activation and concomitant resistance to cell death in CD28-deficient HLA-DQ8 transgenic mice
1 Department of Immunology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Correspondence to: C. S. David; E-mail: davic4{at}mayo.edu
Transmitting editor: G. J. Hämmerling
HLA class II molecules present superantigens more efficiently than their murine counterpart. Therefore, transgenic mice expressing HLA-DQ8 with and without CD28 were used to address the role of CD28 in staphylococcal enterotoxin B (SEB)-driven immune responses. SEB-induced in vitro proliferation of naive DQ8.CD28–/– splenocytes was comparable to DQ8.CD28+/+ cells, and was several fold higher than that of C57BL/10 and BALB/c splenocytes. SEB-activated, naive DQ8.CD28–/– cells in vitro produced significantly less IL-2, IL-4 and IL-10 than DQ8.CD28+/+ cells, while IFN-
and IL-6 production was comparable. SEB-induced in vivo expansion of CD4+ T cells and, to a greater extent, CD8+ T cells was compromised in DQ8.CD28–/– mice, indicating that SEB-induced proliferation of CD8+ T cells is more dependent on CD28 co-stimulation. Upon re-stimulation, SEB-primed CD28+/+ T cells failed to proliferate but were capable of producing cytokines. Conversely, CD28–/– T cells were capable of proliferation, but not cytokine production. SEB-primed CD28-deficient cells produced significantly less nitric oxide when compared to CD28-sufficient cells following re-stimulation with SEB. CD28+/+ and not CD28–/– mice were highly susceptible to SEB-induced lethal shock characterized by significantly elevated serum IFN-. Thus, (i) efficient presentation of SEB by HLA-DQ8 circumvents co-stimulation through CD28, (ii) unique CD28-derived signals are mandatory for generation of certain effector functions, and (iii) absence of CD28-derived signals confers resistance to activation-induced cell death and protects mice from SEB-induced shock.
Keywords: co-stimulatory molecule, MHC, rodent, superantigen, transgenic/knockout
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