Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB / c mice.
Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.
Maillard
I
I
Institute of Microbiology, University of Lausanne, Lausanne, Switzerland.
Launois
P
P
Himmelrich
H
H
Acha-Orbea
H
H
Diggelmann
H
H
Locksley
R M
RM
Louis
J A
JA
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000953:Antigens, Protozoan; D002454:Cell Differentiation / Q000187:drug effects; D022801:Complementarity Determining Regions / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018089:Superantigens / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation
D000906:Antibodies; D000953:Antigens, Protozoan; D022801:Complementarity Determining Regions; D015800:Protozoan Proteins; D012333:RNA, Messenger; D018089:Superantigens; C093139:LACK antigen, Leishmania; D015847:Interleukin-4; D007371:Interferon-gamma