Effect of Polyinosinic-polycytidylic Acid on Humoral and Cellular Immunity

Abstract

Experiments have been performed to investigate the effects of polyinosinic-polycytidylic acid (Poly I:C) on humoral and cellular immunity in RFM/Un mice. Poly I:C, 0.1 mg i.p., administered 48 and 24 hours before 4 x 10⁸ SRBC produced a marked reduction in direct PFC/10⁶ cells and /spleen, and in the hemoagglutinin titre on the 3rd, 4th and 5th days after antigen inoculation. On the other hand, an increase in PFC and hemoagglutinin titre was observed on the 7th and 8th days. Histological examination revealed absence of germinal centers in the spleen on the 4th day. Poly I:C administered 24 and 48 hours after antigen produced an increase in direct PFC and hemoagglutinin titre on the 4th, 5th and 6th day. Histological examination disclosed evident germinal centers in the spleen on the 4th day after antigen. Poly I:C administered 5 to 1 days before antigen produced a markedly depressed direct PFC response in the groups injected 1 and 2 days before antigen. Recovery of the immune response was progressive and complete in groups injected 4 days before antigen. To study the effect of Poly I:C on secondary response to SRBC, two groups of animals injected with Poly I:C before or after antigen were reinjected with 2 x 10⁸ SRBC. Secondary response evaluated by hemoagglutinin titre at varying intervals after the immunization disclosed in both groups a much higher antibody titre than that seen in controls receiving SRBC only. Mice injected with Poly I:C 48 or 24 hours before reimmunization with 2 x 10⁸ SRBC were no different from controls on 3rd and 4th days in regard to number of indirect PFC as well as hemoagglutinin titre. Finally, mice immunized with two SRBC injections and then treated with Poly I:C on alternating days for 30 days had a much higher titre of hemoagglutinins than controls. In order to study the effect of Poly I:C on the cellular immune response, spleen cells from animals receiving Poly I:C 6–5 days before sacrifice were cultured in vitro with phytohemoagglutinin. DNA synthesis subsequent to PHA stimulation was evaluated by increase in 3HTdR incorporation. Cells from animals which had received Poly I:C demonstrated a remarkably higher 3HTdR uptake than cells from control animals. On the other hand, 5 x 10⁶ spleen cells obtained from RFM/Un mice injected with Poly I:C as above were inoculated in 1–4 day old (RFM/Un x CBA/H)F₁ hybrids. These were then sacrificed on day 8 and spleen indices calculated. Experimental animals disclosed GVH activity similar to that of controls (spleen index 2.3). From the results it is clear that if Poly I:C is injected before antigen the primary immune response is deppressed, whereas it is enhanced when Poly I:C is administered after antigen. On the other hand, the secondary response is generally enhanced regardless of the time of Poly I:C administration. Moreover, in Poly I:C –- treated animals there is an enhancement of PHA –- responsive cells while the GVH reactions is unchanged. As Poly I:C is capable of enhancing immune reactivity, the possibility of its use in antineoplastic chemotherapeutic protocols is suggested.