Page 596 - Veterinary Immunology, 10th Edition

cytomegalovirus. Because NK cells employ multiple activating
VetBooks.ir receptors, an NK cell activated through one receptor may well be

reactivated through a different receptor. For example, NK cells
initially activated through Ly49 may be reactivated through

NKG2D. This NK “memory” response could be more accurately
described as training rather than memory.

NK Cell Subsets

NK cell subsets have been identified in many species. Some of these
subsets may simply represent cells at different stages of

development. Some NK cell diversity probably reflects site-specific
subpopulations such as those found in the liver or the thymus. NK
phenotypes may also change with age. In mice some NK cells

express Ly49, whereas others do not. In humans, some subsets
differentially express CD56 and CD16. Cells that express both are
primarily cytotoxic, whereas those that express CD56 in the absence
of CD16 are mainly cytokine producers. This second population
predominates in secondary lymphoid organs. In humans, there is

also evidence of two NK subsets based on cytokine secretion. NK1
cells produce IFN-γ but almost no IL-4, IL-10, or IL-13. NK2 cells do
not secrete IFN-γ but produce IL-13. Another subset of NK cells has

a regulatory function, secretes IL-10, and dampens immune
responses. It has been suggested that NK cells exposed to moderate
levels of IL-12 secrete IFN-γ, but if exposed to very high levels of
IL-12, they produce IL-10 that can then suppress T cell activities. In
effect, overstimulation turns on a suppressive function. These

regulatory NK cells may reduce the severity of virus-induced
immunopathology.

Species Differences

Mammalian NK cell expression of KIR and Ly49 receptors is species

specific and mutually exclusive. A species may have either a
diverse Ly49 or a diverse KIR gene family, but not both. For
example, humans have multiple polymorphic KIR genes but only a
single, nonfunctional Ly49 gene. Likewise, cattle, dogs, cats, and

pigs also possess multiple KIR genes and a single functional Ly49
gene. This suggests that the use of multiple Ly49 genes by rodents
and horses is not typical of mammals in general (Fig. 19.12).

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