Department of Pathology
Animals; Antigens, CD; Antigens, Differentiation; *Antigens, Ly; Carrier Proteins; H-2 Antigens; Homeostasis; *Immunoconjugates; Killer Cells, Natural; Lectins, C-Type; Lymphocyte Activation; Lymphoproliferative Disorders; Membrane Proteins; Mice; Mice, Knockout; Receptors, Immunologic; Signal Transduction; T-Lymphocytes
Immunology and Infectious Disease | Medical Pathology
T-cell responses are regulated by activating and inhibiting signals. CD28 and its homologue, cytotoxic T-lymphocyte antigen 4 (CTLA-4), are the primary regulatory molecules that enhance or inhibit T-cell activation, respectively. Recently it has been shown that inhibitory natural killer (NK) cell receptors (NKRs) are expressed on subsets of T cells. It has been proposed that these receptors may also play an important role in regulating T-cell responses. However, the extent to which the NKRs modulate peripheral T-cell homeostasis and activation in vivo remains unclear. In this report we show that NK cell inhibitory receptor Ly49A engagement on T cells dramatically limits T-cell activation and the resultant lymphoproliferative disorder that occurs in CTLA-4-deficient mice. Prevention of activation and expansion of the potentially autoreactive CTLA-4(-/-) T cells by the Ly49A-mediated inhibitory signal demonstrates that NKR expression can play an important regulatory role in T-cell homeostasis in vivo. These results demonstrate the importance of inhibitory signals in T-cell homeostasis and suggest the common biochemical basis of inhibitory signaling pathways in T lymphocytes.
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Citation: Blood. 2002 Jun 15;99(12):4509-16.