title: Mutual helper effect in copulsing of dendritic cells with 2 antigens: a novel approach for improvement of dendritic-based vaccine efficacy against tumors and infectious diseases simultaneously.
abstract: To develop an efficient dendritic cell (DC)-based immunotherapy protocol, we examined whether simultaneous pulsing of DCs with a given antigen and a third-party antigen could enhance their antigen presentation capacity. Purified splenic DCs of Balb/c mice were pulsed separately with immunoglobulin G, ovalbumin, conalbumin, P15 peptide of Mycobacterium tuberculosis, and prostate-specific antigen or double combinations of the aforementioned antigens. In some settings, DCs pulsed with 1 antigen were mixed equally with those pulsed with another antigen. Antigen-pulsed DCs were injected into the footpad of syngeneic mice and proliferation of whole, CD4 and CD8 depleted lymph node cells was measured after restimulation with cognate antigen. Antigen-specific production of interferon-gamma (IFNgamma) was tested in culture supernatants. Frequency of responding lymph node cells was determined by IFNgamma enzyme-linked immunosorbent spot assay. Our results showed that copulsing of DCs with 2 unrelated antigens increased the capacity of DCs to induce antigen-specific T-cell proliferation against both antigens up to 16-fold. Injection of 2 populations of DCs each pulsed with a different antigen, increased proliferation of primed T cells significantly as well. Both CD4 and CD8 depleted populations showed vigorous proliferative response in copulsing system. In addition, copulsing of DCs with 2 antigens resulted in higher frequency of antigen-specific responding cells and significantly more IFNgamma production. Our results clearly showed that unrelated peptides and proteins could be used to enhance efficacy of DC-based vaccines and in this system, each antigen served to help the other one, a condition that we termed as "mutual helper effect."
authors.affiliation: Department of Reproductive Immunology, Reproductive Biotechnology Research Center, Avicenna Research Institute, Shahid Beheshti University, Evin, Tehran, Iran.
authors.forename: Jaleh
authors.initials: J
authors.lastname: Shojaeian
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.forename: Pouneh
authors.initials: P
authors.lastname: Dokouhaki
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Mahmoudi
authors.forename: Roya
authors.initials: R
authors.lastname: Ghods
authors.forename: Mahmood
authors.initials: M
authors.lastname: Bozorgmehr
authors.forename: Shohreh
authors.initials: S
authors.lastname: Nikoo
authors.forename: Ali Ahmad
authors.initials: AA
authors.lastname: Bayat
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Akhondi
authors.forename: Mahyar
authors.initials: M
authors.lastname: Ostadkarampour
authors.forename: Simin
authors.initials: S
authors.lastname: Rezania
authors.forename: Amir Hassan
authors.initials: AH
authors.lastname: Zarnani