Functional and Genetic Analysis of Two CD8 T Cell Subsets Defined by the Level of CD45RC Expression in the Rat

Abstract

Differential cytokine production by T cells plays an important role in the outcome of the immune response. We show that the level of CD45RC expression differentiates rat CD8 T cells in two subpopulations, CD45RChigh and CD45RClow, that have different cytokine profiles and functions. Upon in vitro stimulation, in an Ag-presenting cell-independent system, CD45RChigh CD8 T cells produce IL-2 and IFN-γ while CD45RClow CD8 T cells produce IL-4, IL-10, and IL-13. In vitro, these subsets also exhibit different cytotoxic and suppressive functions. The CD45RChigh/CD45RClow CD8 T cell ratio was determined in Lewis (LEW) and Brown-Norway (BN) rats. These two rat strains differ with respect to the Th1/Th2 polarization of their immune responses and to their susceptibility to develop distinct immune diseases. The CD45RChigh/CD45RClow CD8 T cell ratio is higher in LEW than in BN rats, and this difference is dependent on hemopoietic cells. Linkage analysis in a F2(LEW × BN) intercross identified two quantitative trait loci on chromosomes 9 and 20 controlling the CD45RChigh/CD45RClow CD8 T cell ratio. This genetic control was confirmed in congenic rats. The region on chromosome 9 was narrowed down to a 1.2-cM interval that was found to also control the IgE response in a model of Th2-mediated disorder. Identification of genes that control the CD45RChigh/CD45RClow CD8 T cell subsets in these regions could be of great interest for the understanding of the pathophysiology of immune-mediated diseases.

Unusual case presentations associated with the CD45 C77G polymorphism

“…Severe salmonella infections can be associated also with polymorphisms of the IL-12/IFN-g cytokine system but the patient had normal numbers of IFN-g-producing cells, making it unlikely that this is the cause of the disease [45]. However, as mentioned above, abnormal CD45 expression is associated in animals and in individuals with both C77G and the less well-studied A138G polymorphism, with altered cytokine production [21][22][23]28,37,38].…”

“…Nor, although there are several syndromes associating cardiac and immunological abnormalities [35,36], do we have any information on the clinical status of the patient, as we could not obtain this for ethical reasons. Discovery of C77G in all these patients may be an incidental finding but the evidence that immune function is abnormal in humans and experimental animals with altered CD45 expression suggests that these polymorphisms may contribute to disease pathogenesis [21][22][23]28,37,38].…”

Altered lipid raft–associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus

“…Thus, whereas CD45RC low are short-lived memory cells that orchestrate rapid kinetics, CD45RC high are longlived cells that ensure the endurance of immunologic memory (47). Furthermore, rat CD45RC high and CD45RC low CD8 cells have also been shown to have different cytokine profiles and functions (48).…”

FOXP3+ regulatory T cells: Current controversies and future perspectives

“…Not only do some regulatory cells express CD8 rather than CD4 [3], but CD25 has limitations as it is not T cell restricted and cannot be used to distinguish Treg from activated effector T cells (Teff). While the murine CD4 + CD25 + population is relatively homogenous and is highly enriched in Treg, in humans CD25 + cells contain both Treg and Teff populations (Fig.…”