Immune response to allogenic tumor cells is associated with the appearance of long-living CD8+ memory cells capable of rapid restimulation and lysis of tumor cells in case of repeated injection of these cells. In order to acquire the effector function, allorestricted memory cells need antigen restimulation for 2 days, which is a specific feature of central memory cell population. These cells can suppress proliferation of naive splenocytes in vitro. In mixed lymphocyte cultures containing memory cells, antigen stimulation induces more intensive IL-10 production and deeper suppression of IL-2 production in comparison with cultures containing naive cells. The conditions for activation of naive cells during secondary immune response are not optimal.

Experiments on mice deficient in expression of class I major histocompatibility complex molecules showed that memory CD8+ cells recognizing the alloantigen by the direct allogeneic recognition mechanism selectively proliferated in response to heated allogeneic cells. Adoptive transfer of memory cells from mice expressing green fluorescent protein transgene to wild-type animals showed for the first time that long-living memory cells suppress the response of naive T cells and abolish their involvement in the pool of memory cells. The pool of long-living memory T cells was obtained in vitro with heated allogeneic stimulators. Apart from immunizing alloantigen, this clone recognized foreign molecules of the major histocompatibility complex. Cloning and sequencing of rearranged regions in memory T cells showed that two alpha-chains and one functional beta-chain are rearranged in cells of this pool. Only one alpha-chain was capable of forming protein product, which determines expression of only one form of T cell receptor. Experimental data directly confirm the hypothesis about degeneracy of recognition of allelic products of major histocompatibility complex molecules by T cell receptors. Suppression of the response of naive cells by memory cells probably underlies a previously unknown type of polarization of the immune response and determines clonal dominance and peripheral selection of T lymphocytes.

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