Cutting Edge: Precursor Frequency Affects the Helper Dependence of Cytotoxic T Cells1

Generation of CTL immunity often depends on the availability of CD4 T cell help. In this report, we show that CTL responses induced by cross-priming can be converted from CD4-dependent to CD4-independent by increasing the frequency of CTL precursors. In the absence of CD4 T cells, high numbers of CTL precursors were able to expand in number and become effector CTL. The ability of high frequencies of CD8 T cells to override help was not due to their ability to signal CD40 via expression of CD154. These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help.

[1]  C. Kurts,et al.  Characterization of the ovalbumin‐specific TCR transgenic line OT‐I: MHC elements for positive and negative selection , 2000, Immunology and cell biology.

[2]  D. Pardoll,et al.  Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes , 2000, The Journal of experimental medicine.

[3]  A. Suhrbier,et al.  Effect of pre‐existing cytotoxic T lymphocytes on therapeutic vaccines , 2000, European journal of immunology.

[4]  L. Lefrançois,et al.  A Critical Role for Cd40–Cd40 Ligand Interactions in Amplification of the Mucosal Cd8 T Cell Response , 1999, The Journal of experimental medicine.

[5]  M. Bachmann,et al.  CD8+ T Cells Mediate CD40-independent Maturation of Dendritic Cells In Vivo , 1999, The Journal of experimental medicine.

[6]  R. Steinman,et al.  TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation , 1999, The Journal of experimental medicine.

[7]  Richard A. Flavell,et al.  Help for cytotoxic-T-cell responses is mediated by CD40 signalling , 1998, Nature.

[8]  Polly Matzinger,et al.  A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell , 1998, Nature.

[9]  Stephen P. Schoenberger,et al.  T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions , 1998, Nature.

[10]  J. Altman,et al.  Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. , 1998, Immunity.

[11]  C. Kurts,et al.  Class I–restricted Cross-Presentation of Exogenous Self-Antigens Leads to Deletion of Autoreactive CD8+ T Cells , 1997, The Journal of experimental medicine.

[12]  W. Heath,et al.  Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help , 1997, The Journal of experimental medicine.

[13]  T. Mosmann,et al.  Cytotoxicity and weak CD40 ligand expression of CD8+ type 2 cytotoxic T cells restricts their potential B cell helper activity , 1997, European journal of immunology.

[14]  P. Doherty,et al.  Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells , 1996, The Journal of experimental medicine.

[15]  J. Miller,et al.  Constitutive class I-restricted exogenous presentation of self antigens in vivo , 1996, The Journal of experimental medicine.

[16]  M. V. von Herrath,et al.  CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge , 1996, Journal of virology.

[17]  J. Banchereau,et al.  CD40 ligand‐positive CD8+ T cell clones allow B cell growth and differentiation , 1995, European journal of immunology.

[18]  F. Fitch,et al.  IL-4-producing CD8+ T cell clones can provide B cell help. , 1995, Journal of immunology.

[19]  Kristin A. Hogquist,et al.  T cell receptor antagonist peptides induce positive selection , 1994, Cell.

[20]  H. von Boehmer,et al.  CD4+8− help prevents rapid deletion of CD8+ cells after a transient response to antigen , 1993, European journal of immunology.

[21]  M. Bevan,et al.  Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture , 1993, The Journal of experimental medicine.

[22]  G. Schönrich,et al.  Autoimmune diabetes as a consequence of locally produced interleukin-2 , 1992, Nature.

[23]  P. Matzinger,et al.  A fail-safe mechanism for maintaining self-tolerance , 1992, The Journal of experimental medicine.

[24]  H. Pircher,et al.  Preferential positive selection of Vα2+CD8+ T cells in mouse strains expressing both H‐2k and T cell receptor Vαa haplotypes: determination with a Vα2‐specific monoclonal antibody , 1992, European journal of immunology.

[25]  M. Schilham,et al.  Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4 , 1991, Nature.

[26]  D. Gray,et al.  Mice lacking MHC class II molecules , 1991, Cell.

[27]  M. Bevan,et al.  Class I-restricted processing and presentation of exogenous cell- associated antigen in vivo , 1990, The Journal of experimental medicine.

[28]  A. Müllbacher,et al.  The generation and activation of memory class I MHC restricted cytotoxic T cell responses to influenza A virus in vivo do not require CD4+ T cells , 1989, Immunology and cell biology.

[29]  L. Husmann,et al.  Cooperation between Helper T Cells and Cytotoxic T Lymphocyte Precursors , 1988, Annals of the New York Academy of Sciences.

[30]  R. Buller,et al.  Induction of cytotoxic T-cell responses in vivo in the absence of CD4 helper cells , 1987, Nature.

[31]  J. Forman,et al.  Helper activity is required for the in vivo generation of cytotoxic T lymphocytes , 1982, The Journal of experimental medicine.

[32]  P. Doherty,et al.  Progressive Loss of Cd8 + T Cell-mediated Control of a ~/-herpesvirus in the Absence of Cd4 + T Cells , 1996 .

[33]  Melinda Fitzgerald,et al.  Immunol. Cell Biol. , 1995 .

[34]  E. Palmer,et al.  Class I and class II MHC gene products differentially affect the fate of V beta 5 bearing thymocytes. , 1990, The Journal of molecular and cellular immunology : JMCI.