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J. Exp. Med.,
Volume 187, Number 7, April 6, 1998 1151-1156
By
From the Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan
Comprehensive Cancer Center, New York University Medical Center, New York 10016
It is well established that B7-CD28/CTLA4 interactions play an important role in the induction of T helper cells for T-dependent antibody responses. However, targeted mutation of
CD28 does not significantly affect production of IgG and activation of CD4 T helper cells in
response to infections by some viruses and nematode parasites. To test whether the CD28-independent induction of Ig class switches requires costimulation by the heat-stable antigen (HSA), we compared T helper cell induction and antibody response in mice deficient for either
HSA, CD28, or both genes. We found that after immunization with KLH-DNP, mice deficient for both CD28 and HSA lack DNP-specific IgA and all subtypes of IgG. This deficiency
corresponds to a reduced number of effector helper T cells that rapidly produce IL-2, IL-4, and
IFN-
after in vitro stimulation with carrier antigen KLH. In contrast, priming of T helper
cells and Ig class switch are normal in mice deficient with either HSA or CD28 alone. IgM responses are not affected by any of these targeted mutations. These results demonstrate that
CD28-independent induction of T helper cells and Ig class-switches requires costimulation by
the HSA.
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