Evaluation of the Role of C4 in the Cellular Immune Response in Vitro

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Abstract
The demonstration that antisera to human C4 inhibit the human mixed lymphocyte reaction and the response to the mitogen, phytohemagglutin, suggested a possible role of C4 in the afferent phase of immune recognition. An attempt was made to reproduce and extend these observations in the guinea pig. Monospecific antisera to C4 were raised in C4-deficient guinea pigs, rabbit, or goat. The antisera were tested for inhibition of the unidirectional mixed leukocyte reactions between strain 13 and strain 2 guinea pigs, for inhibition of proliferation induced by the mitogens, phytohemagglutinin and concanavalin A, and for inhibition of the proliferative response of immune T lymphocytes to soluble protein antigens. In a large number of experiments no reproducible inhibition was found when the various cultures were performed in the presence of antiserum to C4. Furthermore, lymphocytes from C4-deficient guinea pigs responded as well as lymphocytes from strain 13 animals to specific antigen or in mitogen-induced proliferation, indicating a normal capacity of T cells from C4-deficient animals for recognition of antigen or mitogen and for proliferation. Antigen- or mitogen-pulsed macrophages from C4-deficient guinea pigs were able to effectively stimulate T cell proliferation, suggesting a normal capability for antigen or mitogen presentation. These data argue against a possible role for C4 in antigen, mitogen, or alloantigen-induced T lymphocyte activation and indicate that the demonstrated functional association of C4 and MHC-mediated reactions in the human does not generally apply to another species.

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