Collaboration of helper and cytotoxic T lymphocytes

Abstract

Cytotoxic T lymphocytes are major effector cells in response to viral infections and in allograft rejection and are implicated in many other immunological reactions. Efficient induction of cytotoxic activity in these cells in many but not all cases depends upon helper T and antigen-presenting cells so that at least three different cell types have to work together. Here we present an in vitro model for the helper T cell-dependent induction of cytotoxic T lymphocytes which allows the investigation of the collaboration of helper and cytotoxic T cells. First results demonstrate that linkage of helper and killer epitopes on the surface of one antigen-presenting cell is a prerequisite for productive interaction between the two T cells that results in induction of cytolytic activity. T helper 1 and T helper 2 cells are equally efficient. The crucial roles of interleukin-2 and interferon-gamma in this process were confirmed. Activated CD4 cells can influence cytotoxic T lymphocytes in such a way that they produce interferon-gamma independent from recognition of cognate peptide. The possibility of direct T-T contacts mediated by adhesion molecules that promote collaboration of the two cells is discussed.

Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C

“…CD4 ϩ (Th1) cells have been shown in vitro to promote the generation of CTLs, likely through the production of IL-2 and IFN-␥. 27,28 The influence of the HCV-specific CD4 ϩ response on HCV-specific CTL and sensitivity to IFN therapy awaits further investigation.…”

Potent CTL Induction by a Whole Cell Pertussis Vaccine in Anti‐Tumor Peptide Immunotherapy

“…Normally, a Th-CTL epitope linkage, i.e. a simultaneous presentation of both Th and CTL epitopes derived from the same antigen on the same APC, is desirable when the amount of antigen is limited, probably due to better cell-cell interaction (57). However, if strongly activated, Th cells can stimulate, in trans, other T cells and B cells in the vicinity that are specific for heterologous antigens through soluble mediators.…”

Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS

“…immunocompetent individuals, as their CD4 cells react Thus, we have investigated whether antigen-specific to intracellular pathogens, 8 produce lymphokines capable CD4 cells from normal and from seropositive donors can of restraining the growth of fungi and protozoa, 9,10 and be transduced with a retroviral vector carrying an antiprovide help for clonal expansion of B cells 9 as well as of tat antisense tRNA gene 20 to be made resistant to HIV-1 CD8 cytotoxic cells. 11,12 Therefore, any treatment of AIDS replication, while maintaining their functional properties. should aim at restoring the immune repertoire that enables the patient to withstand opportunistic infections.…”