Others have shown that pristane induced arthritis (P.I.A.) in H-2k CBA mice can be inhibited by preimmunizing mice with Mycobacterial (Mt) heat shock protein 65 (hsp65) or with a synthetic immunodominant peptide 261-271 derived from Mt hsp65 administered in Incomplete Freund's Adjuvants (IFA). We preimmunized H-2d BALB/c.D2-Idh-Pep3 mice with Mt hsp65 peptide 261-271 in IFA and found that preimmunization can prolong the latent period and reduces the incidence of PCTs, but the results were not consistent. We are refining the induction protocols and methods of immunization, including other antigen to improve this inhibitory effect. All the preimmunizations thus far utilize IFA, which by itself enhances and accelerates PCT development. We now explore immunization with DNA plasmids coding for hsp65. Hypothesizing that BALB/c mice fail to develop Tn1 responses to important natural antigens, we are preparing to test genetically altered mice that upregulate Tn1 responses. BALB/c.IL-6 Tg mice develop a dramatic plasma cell hyperplasia in lymph nodes and spleen, and 50 percent develop PCTs. When BALB/c.IL-6 Tg mice are crossed with BALB/c.BCL XL Tg mice, 90 percent develop PCTs spontaneously between 70-100 days. Further, when BCL XL mice are given pristane, they develop PCTs 60-90 days later. These two protocols have provided an accelerated model of PCT formation, and we now will determine if these tumors involve the bone marrow.
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