EFFECT OF INVIVO ADMINISTRATION OF RECOMBINANT MURINE GAMMA INTERFERON ON INVITRO LYMPHOPROLIFERATIVE RESPONSES FOLLOWING IMMUNIZATION WITH CANDIDA-ALBICANS

The effect of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) on in vitro proliferation of lymphocytes to Candida antigens and lectins was examined in naive CBA/J mice and in similar mice colonized with Candida albicans by intragastric (i.g.) intubation and/or inoculated intradermally (i.d.) with the fungus. Lymph node lymphocyte and splenic lymphocyte (splenocyte) responses to soluble cytoplasmic substances derived from C. albicans varied with the route of inoculation of the fungus, the sex of the animal, and the presence or absence of rMuIFN-gamma treatment. In the absence of rMuIFN-gamma treatment, lymphoid cells from lymph nodes draining the site of the i.d. lesion responded well to soluble cytoplasmic substances. Colonization of the gut of female mice with C. albicans either had no effect or promoted better lymph node responses when such animals were also challenged i.d., whereas gut colonization of males followed by i.d. challenge appeared to have a suppressive influence on the level of proliferation in response to antigens in vitro. Antigen-specific splenocyte responses could be detected as well, and they were best in animals inoculated i.g.-i.d. or i.d. only. With the exception of lymph node lymphocytes from male mice, treatment of infected animals, regardless of the route of infection, with rMuIFN-gamma frequently resulted in lowered responses to antigens when comparable treatment groups were examined. With respect to mitogen stimulation, infection with C. albicans, especially i.g. or i.g.-i.d., resulted in a population of lymph node lymphocytes with lower-than-normal responses to concanavalin A but higher-than-normal responses to lipopolysaccharide (LPS). Splenocyte responses to mitogens were not altered as dramatically as the responses of lymph node lymphocytes, but splenocytes from female mice had a suppressed response regardless of the route of exposure to C. albicans, and those from mice which were maximally stimulated with C. albicans, i.e., inoculated i.g.-i.d., also had a suppressed response to concanavalin A. Treatment with rMuIFN-gamma either had no effect on the subsequent splenocyte responses or boosted subnormal mitogen responses toward the normal range. Collectively, these data illustrate that exposure to both C. albicans and rMuIFN-gamma influenced the responses to mitogen and C. albicans antigen of lymph node lymphocyte and splenocyte populations, as detected in vitro by lymphoproliferation. Treatment with rMuIFN-gamma often resulted in increased responsiveness to a B cell mitogen, LPS, and decreased responsiveness to a C. albicans antigen.