Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.
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Defining the Signature of VISTA on Myeloid Cell Chemokine ResponsivenessTWK Broughton et al. Front Immunol 10, 2641. PMID 31803182.The role of negative checkpoint regulators (NCRs) in human health and disease cannot be overstated. V-domain Ig-containing Suppressor of T-cell Activation (VISTA) is an I …
Disruption of the Immune-Checkpoint VISTA Gene Imparts a Proinflammatory Phenotype With Predisposition to the Development of AutoimmunityL Wang et al. Proc Natl Acad Sci U S A 111 (41), 14846-51. PMID 25267631.V domain-containing Ig suppressor of T-cell activation (VISTA) is a negative checkpoint regulator that suppresses T cell-mediated immune responses. Previous studies using …
Immune-checkpoint Proteins VISTA and PD-1 Nonredundantly Regulate Murine T-cell ResponsesJ Liu et al. Proc Natl Acad Sci U S A 112 (21), 6682-7. PMID 25964334.V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a negative immune-checkpoint protein that suppresses T-cell responses. To determine whether VISTA syner …
A New VISTA on Combination Therapy for Negative Checkpoint Regulator BlockadeJ Deng et al. J Immunother Cancer 4, 86. PMID 28031817. - ReviewNegative checkpoint regulators function to restrain T cell responses to maintain tolerance and limit immunopathology. However, in the setting of malignancy, these pathway …
VISTA: A Novel Immunotherapy Target for Normalizing Innate and Adaptive ImmunityMA ElTanbouly et al. Semin Immunol 42, 101308. PMID 31604531. - ReviewV-domain Ig suppressor of T cell activation (VISTA) is a novel checkpoint regulator with limited homology to other B7 family members. The constitutive expression of VISTA …