Abstract
Teleost fish express highly diverse naive TCRβ (TRB) repertoires and mount strong public and private clonal responses upon infection with pathogens. Fish T cells express typical markers such as CD8, CD4-1 and CD4-2, CD3, CD28 and CTLA4. Fish CD8+ T cells have been shown to be responsible for antigen-specific cell-mediated cytotoxicity in in vitro systems using histo-compatible effector and target cells. We compare here the complexity of TRB repertoires between FACS sorted CD8+ and CD8− T cells from spleen and pronephros of rainbow trout. In contrast to human, while the TRB repertoire is highly diverse and polyclonal in CD8+ T cells of naïve fish, it appeared very different in CD8− lymphocytes with irregular CDR3 length distributions suggesting a dominance of activated clones already in naïve fish or the presence of non conventional T cells. After infection with a systemic virus, CD8+ T cells mount a typical response with significant skewing of CDR3 length profiles. The infection also induces significant modifications of the TRB repertoire expressed by the CD8− fraction, but for a different set of V/J combinations. In this fraction, the antiviral response results in an increase of the peak diversity of spectratypes. This unusual observation reflects the presence of a number of T cell expansions that rise the relative importance of minor peaks of the highly skewed distributions observed in unchallenged animals. These results suggest that the diversity of TRB expressed by CD8+ and CD8− αβ T cells may be subjected to different regulatory patterns in fish and in mammals.
Highlights
The adaptive immune response to infectious agents is characterized by initial priming and expansion of T and B cell clones specific of the pathogen
Since the expression of the rainbow trout CD8 co-receptor appears to be correlated with T cell cytotoxic activity, we undertook the analysis of the TRB-repertoire of FACS-sorted CD8+ and CD82 cell subsets to compare the respective T cell antigen-specific receptor (TR) diversity of cytotoxic and other ab T cells in fish
It is highly restricted by the Major Histocompatibility complex (MHC) alleles expressed by the individual, as well as antigen-driven T cell responses occurring in periphery
Summary
The adaptive immune response to infectious agents is characterized by initial priming and expansion of T and B cell clones specific of the pathogen. The variable domain is highly diverse due to somatic rearrangements in variable (V), joining (J), and, in the case of the b or d-chain, diversity (D) segments, occurring during T cell differentiation. This large diversity allows a specific recognition of any antigen by a few T cell clones in an individual, leading to activation and clonal expansion. The dynamics of antigen-specific lymphocyte responses in vivo during the course of infection follows a general pattern: the initial expansion of effector cells precedes a rapid contraction phase, leaving a relatively stable, small pool of memory cells that provide long-term immunity
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