Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity

Henning, Golo; Kraft, Michael S.; Derfuss, Tobias; Pirzer, Rainer; Basile, Geneviève de Saint; Aversa, Gregorio; Fleckenstein, Bernhard; Meinl, Edgar

doi:10.1002/1521-4141(200109)31:9<2741::aid-immu2741>3.0.co;2-6

Cited by 43 publications

(24 citation statements)

References 36 publications

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“…The activation markers CD25, CD69, CD56 are normally up-regulated in SAPdeficient CD8 ϩ T cells following activation through the TCR or with IL-15. Furthermore, the SAP-interacting receptors SLAM, 2B4, and CD84, which costimulate lytic activity, 15,30 are normally expressed in resting or activated CD8 ϩ T cells from SAP-deficient patients. These results show that SAP deficiency does not impair the expression of these receptors.…”

Section: Discussionmentioning

confidence: 99%

“…SLAM is expressed on activated and memory T cells, in which it can skew cytokine production toward a T helper 1 (Th1) profile 14 and can act as a costimulatory molecule for cytotoxic activity. 15 SAP appears to be a natural inhibitor of the interaction of SLAM-family members with SH2-containing signal molecules such as the SH2-containing phosphatase 2 (SHP-2) phosphatase. 2 In T cells, SAP recruits FynT, which is required for SLAM phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells

Dupré

Andolfi

Tangye

et al. 2005

Blood

158

137

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IntroductionX-linked lymphoproliferative (XLP) disease is a severe immunodeficiency characterized by variable clinical phenotypes, including fatal infectious mononucleosis, malignant B-cell lymphoma, and progressive dysgammaglobulinemia. 1 The gene responsible for XLP (SH2D1A) encodes for SAP (SLAM [signaling lymphocyteactivation molecule]-associated protein), or SH2D1A, a natural killer (NK) and T-cell-specific signaling adaptor protein. [2][3][4] Mutations in the SH2D1A gene have been detected in patients with hemophagocytic lymphohistiocytosis (HLH) 5 and common variable immunodeficiency syndrome, 6,7 thereby expanding the range of clinical phenotypes associated with this genetic defect. These heterogeneous clinical manifestations might be related to viral infections, which appear to act as secondary factors triggering the severe forms of SAP-deficiency syndrome. In the absence of SAP, dysregulation of T/B-cell interactions and NK-cell functions has been proposed to result in a variable ability to control Epstein-Barr virus (EBV) infection, leading to either fatal infectious mononucleosis, or infectious mononucleosis with progression toward malignant B-cell lymphoma or acquired agammaglobulinemia. 8 However, in some patients with XLP, these manifestations can also occur in the absence of EBV infection. 9 SAP is a protein of 128 residues with a single Src homology 2 (SH2) domain binding to a consensus T.I/V.(p)Y.x.x.V/I motif on the cytoplasmic tail of surface molecules of the SLAM family, including SLAM, 2B4, CD84, Ly-9, and NTB-A. 2,10-13 These molecules form homotypic and heterotypic receptor-ligand pairs during T cell/antigen-presenting cell or NK cell/target cell contacts. SLAM is expressed on activated and memory T cells, in which it can skew cytokine production toward a T helper 1 (Th1) profile 14 and can act as a costimulatory molecule for cytotoxic activity. 15 SAP appears to be a natural inhibitor of the interaction of SLAM-family members with SH2-containing signal molecules such as the SH2-containing phosphatase 2 (SHP-2) phosphatase. 2 In T cells, SAP recruits FynT, which is required for SLAM phosphorylation. Activation of the SLAM/SAP pathway controls the phosphorylation of dok1, dok2, and SH2-containing inositol phosphatase, thereby playing a potential role in the control of interferon-␥ (IFN-␥) production. 16,17 Furthermore, SAP appears to participate in the adhesion of T cells to target cells, as well as in T-cell receptor (TCR)-mediated activation. 18,19 In SAP-deficient murine models, 20,21 infection with lymphocytic-chorio-meningitis virus is associated with higher mortality related to increased T-cell activation and IFN-␥ production, as well as to a reduction in the production of interleukin 4 (IL-4) and the generation of immunoglobulin-secreting cells. However, in this model, T-and NK-cell cytotoxic activities have not been investigated.A number of studies in patients with XLP indicate that 2B4 stimulation on NK cells induces an abnormal dominant abrogation of NK-cell lytic activity. This ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells

Dupré

Andolfi

Tangye

et al. 2005

Blood

158

137

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show abstract

“…Several investigators observed that, the TCR stimulation in the presence of α-SLAM mAb induced an increase in IFN-γ production (17,19,21) and cytotoxicity of CD8 + T lymphocytes (55). These findings led to the belief that the α-SLAM mAb was agonistic and that its activation regulated the differentiation of T cell, increasing the production of IFN-γ and redirecting the immune response toward a Th1 profile (17,19).…”

Section: The Slam-sap Signaling Pathwaymentioning

confidence: 99%

The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses

Vilar

Frutuoso

Arruda

et al. 2011

Braz J Med Biol Res

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“…T (CD45RO+, CD45RA+, CD4+, CD8+), B ve NK hücrelerde, dentritik hücreler ve makrofajlarda eksprese olur ve ekspresyonu aktivasyonla artar (13,15). AntiSLAM antikorlarıyla uyarıldığında T hücre proliferasyonuna, Th2 hücrelerin Th1 veya Th0 populasyonuna dönüşümüne ve IFNα salınımına neden olur (13,15). Ortamdaki IL-4 düzeyi azalır (13,16,17).…”

Section: ö öZ Ze Et Tunclassified

“…Bu da CD95 aracılı apoptozisi kolaylaştırmaktadır (18). Dentritik hücrelerden inflamatuvar sitokinlerin üretimi ve salınımını arttırır (15,18).…”

Section: ö öZ Ze Et Tunclassified

X'e Bağli Geçi̇ş Gösteren Lenfoproli̇ferati̇f Sendrom: Kli̇ni̇k, Patogenez Ve Geneti̇kle İlgi̇li̇ Geli̇şmeler

Mutlu;İKİNCİOĞULLARI¹

2004

Ankara Üniversitesi Tıp Fakültesi Mecmuası

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Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity

Cited by 43 publications

References 36 publications

SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells

SAP controls the cytolytic activity of CD8+ T cells against EBV-infected cells

The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses

X'e Bağli Geçi̇ş Gösteren Lenfoproli̇ferati̇f Sendrom: Kli̇ni̇k, Patogenez Ve Geneti̇kle İlgi̇li̇ Geli̇şmeler

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