Blockade of CD86 in BALB/c mice infected with Leishmania major does not prevent the expansion of low avidity T cells.
The interactions between CD28 and its ligand CD86 are critical for the regulation of T cell responses. However, it is not clear whether CD4+ T cells expressing low and high avidity TCR are equally dependent on CD28 costimulation for their activation and expansion. To address this issue, we have used multimers of I-Ad molecules linked to a peptide derived from the Leishmania major homolog for the receptor of activated C kinase (LACK) antigen to compare the fate of LACK-specific CD4+ T cells in Leishmania-infected BALB/c mice which have been treated or not with anti-CD86 mAb. Although the administration of anti-CD86 mAb did not completely prevent the expansion of LACK-specific T cells, their frequency and number were markedly reduced. In mice treated with anti-CD86 mAb as well as in control animals, L. major induced the clonal expansion of LACK-specific T cells which expressed a canonical low avidity Valpha8/Vbeta4 TCR. Taken together, our results suggest that the molecular interactions between CD28 on T cells and CD86 on APC serve to amplify and modulate T cell responses without promoting breadth in the TCR repertoire.
Moro
Monica
M
Centre National de la Recherche Scientifique, Valbonne, France.
Filippi
Christophe
C
Gallard
Alexandra
A
Malherbe
Laurent
L
Foucras
Gilles
G
Akiba
Hisaya
H
Yagita
Hideo
H
Guéry
Jean-Charles
JC
Glaichenhaus
Nicolas
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D000953:Antigens, Protozoan; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019674:Genes, T-Cell Receptor beta; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000276:immunology; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000953:Antigens, Protozoan; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C505715:Tnfrsf9 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; C093139:LACK antigen, Leishmania