A superantigen interacts with leishmanial infection in antigen-presenting cells to regulate cytokine commitment of responding CD4 T cells.
Germ-line retroviral insertions in vertebrate genomes are implicated in the modulation of host immune responses. We demonstrate that CBA/J mice, which carry the proviral integrants mammary tumor virus locus 6 (Mtv6) and mammary tumor virus locus 7 (Mtv7), are less resistant to infection with the protozoan pathogen Leishmania major compared with closely related but Mtv6-negative and Mtv7-negative CBA/CaJ mice. Although both strains generated comparable L. major-specific CD4 T cell frequencies, T cells from CBA/J mice made much less interferon γ (IFN-γ). L. major-infected CBA/CaJ dendritic cells primed L. major-specific and allospecific IFN-γ-producing CD4 T cells better in vivo and in vitro, respectively, than CBA/J dendritic cells did. L. major susceptibility appeared to be associated with Mtv7, and v-Sag-7 superantigen expression and L. major infection together reduced the ability of an antigen-presenting cell line to prime alloresponder CD4 T cells for IFN-γ commitment. These data show that an endogenous superantigen can interact with L. major infection to alter antigen-presenting cell properties and modulate T cell cytokine commitment, with implications for human susceptibility to infectious diseases.
Varanasi
Vineeth
V
National Institute of Immunology, New Delhi, India.
Mattoo
Hamid
H
Tupperwar
Nitin C
NC
Thyagarajan
Krishnamurthy
K
Das
Abhishek
A
Kumar
Ramesh
R
Bal
Vineeta
V
Vaidya
Tushar
T
George
Anna
A
Rath
Satyajit
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000276:immunology; D018320:Leishmania major / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D018089:Superantigens / Q000276:immunology*
D000956:Antigens, Viral; D016207:Cytokines; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; D018089:Superantigens; D007371:Interferon-gamma