HIV type 1-induced inhibition of CD45 tyrosine phosphatase activity correlates with disease progression and apoptosis, but not with anti-CD3-induced T cell proliferation.
The tyrosine phosphatase CD45 is a key positive element in multiple lymphocyte signaling pathways. To understand the contribution of CD45 to HIV-1-induced T cell hyporesponsiveness and apoptosis we evaluated the CD45-associated tyrosine phosphatase activity of lymphocytes from patients with different stages of HIV-1 disease and compared it with CD45 expression, spontaneous and Fas-induced apoptosis, anti-CD3-induced T cell proliferation, distribution of CCR5 delta32/wt, and cytokine production. The proliferative response to anti-CD3 as well as the CD45-associated phosphatase activity were significantly reduced in progressors. In long-term nonprogressors (LTNPs) the proliferative response to anti-CD3 was also diminished, although to a lesser extent, while the tyrosine phosphatase activity was not significantly impaired. One-third of LTNPs were found positive for the 32-bp deletion of the CCR5 gene. This mutation had no effects on anti-CD3 proliferative response or CD45 phosphatase activity. A significant reduction in IL-2 and IFN-gamma was observed in both LTNPs and in normal progressors, whereas IL-4 production was significantly decreased only in progressors. Last, we observed a significant correlation between CD45 phosphatase activity and apoptosis. We therefore conclude that the impairment of CD45 tyrosine phosphatase activity correlates with disease progression and the level of T cell apoptosis, but not with anti-CD3-induced T cell proliferation. Moreover, we suggest that evaluation of CD45 tyrosine phosphatase activity may represent an additional tool with which to assess disease progression.
Giovannetti
A
A
Division of Clinical Immunology and Allergy, La Sapienza University of Rome, Italy.
Pierdominici
M
M
Mazzetta
F
F
Mazzone
A M
AM
Ricci
G
G
Prozzo
A
A
Pandolfi
F
F
Paganelli
R
R
Aiuti
F
F
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D016296:Mutagenesis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D019713:Receptors, CCR5 / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D017252:CD3 Complex; D007376:Interleukin-2; D019713:Receptors, CCR5; D019014:fas Receptor; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1