HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation.
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.
Yadav
Anjana
A
Division of Basic Science, Institute of Human Virology, University of Maryland, Rm #S616, 725, West Lombard Street, Baltimore, MD 21201, USA.
Pati
Shibani
S
Nyugen
Anhthu
A
Barabitskaja
Oxana
O
Mondal
Prosanta
P
Anderson
Michael
M
Gallo
Robert C
RC
Huso
David L
DL
Reid
William
W
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D018106:CD28 Antigens / Q000032:analysis / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis / Q000302:isolation & purification; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics; D013997:Time Factors; D051020:bcl-X Protein / Q000096:biosynthesis / Q000302:isolation & purification
C494813:Bcl2l1 protein, rat; D018106:CD28 Antigens; D007376:Interleukin-2; D051020:bcl-X Protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)