RGD Reference Report - HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation. - Rat Genome Database

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HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation.

Authors: Yadav, A  Pati, S  Nyugen, A  Barabitskaja, O  Mondal, P  Anderson, M  Gallo, RC  Huso, DL  Reid, W 
Citation: Yadav A, etal., Virology. 2006 Sep 30;353(2):357-65. Epub 2006 Jul 10.
RGD ID: 1600221
Pubmed: PMID:16828835   (View Abstract at PubMed)
DOI: DOI:10.1016/j.virol.2006.05.026   (Journal Full-text)

Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the alpha/beta T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
human immunodeficiency virus infectious disease  ISOLck (Rattus norvegicus)1600221; 1600221protein:increased tyrosine phosphorylation:T cellRGD 
human immunodeficiency virus infectious disease  IDA 1600221protein:increased tyrosine phosphorylation:T cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lck  (LCK proto-oncogene, Src family tyrosine kinase)

Genes (Mus musculus)
Lck  (lymphocyte protein tyrosine kinase)

Genes (Homo sapiens)
LCK  (LCK proto-oncogene, Src family tyrosine kinase)


Additional Information