Blockade of CD86 in BALB/c mice infected withLeishmania major does not prevent the expansion of low avidity T cells

Abstract

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 Vα8/Vβ4 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.

Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites

“…Evaluation of CMI in human leishmaniasis has focused mainly on cytokine production, and few studies have been performed to characterize the antigenic specificity or the functionality of T-cell populations. In an experimental model of CL, expansion of V␣8-and V␤4-expressing T cells has been related to susceptibility in mice infected with Leishmania major ( 36,43,44). T cells recognize foreign antigens through T-cell antigen receptors (TCRs), and diversity in antigen recognition is generated by ␣ and ␤ genes that rearrange randomly in differentiating T cells.…”