Duality of the murine CD8 compartment.

ABSTRACT: CD8?? plays crucial roles in the thymic selection, differentiation, and activation of some, but not all, CD8(+) T cells, whereas CD8?? does not. To investigate these roles, we produced mice that expressed transgene P14 T-cell receptor ? (TCR?) chain and CD8? or did not (WT and KO mice, respectively). The primary CD8(+) T-cell response to acute lymphocytic choriomeningitis virus (LCMV) infection was predominantly D(b)/GP33 specific and CD8 independent in KO mice and was mostly CD8 dependent in WT mice. Cytotoxic T lymphocytes (CTL) from KO mice failed to mobilize intracellular Ca(2+) and to kill via perforin/granzyme. Their strong Fas/FasL-mediated cytotoxicity and IFN-? response were signaled via a Ca(2+)-independent, PI3K-dependent pathway. This was also true for 15-20% of CD8-independent CTL found in WT mice. Conversely, the perforin/granzyme-mediated killing and IFN-? response of CD8-dependent CTL were signaled via a Ca(2+), p56(lck), and nuclear factor of activated T cells-dependent pathway. Deep sequencing of millions of TCR? chain transcripts revealed that the TCR repertoires of preimmune CD8(+) T cells were highly diverse, but those of LCMV D(b)/GP33-specific CTL, especially from KO mice, were narrow. The immune repertoires exhibited biased use of V? segments that encoded different complementary-determining region 1? (CDR1?) and CDR2? sequences. We suggest that TCR from WT CD8-independent T cells may engage MHC-peptide complexes in a manner unfavorable for efficient CD8 engagement and Ca(2+) signaling but permissive for Ca(2+)-independent, PI3K-dependent signaling. This duality of the CD8 compartment may provide organisms with broader protective immunity.

SUBMITTER: Genolet R 

PROVIDER: S-EPMC3964049 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature