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

Abstract

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.

Involvement of tyrosine phosphatase CD45 in apoptosis

“…The authors suggested that CD3 and CD4 signaling could induce an impaired proliferative response to antigen, anergy and apoptosis induction. The impairment of CD45 tyrosine phosphatase activity correlates with disease progression and the level of T cell apoptosis [121]. Many viral proteins like Tat, Vpr, Nef, gp120 have apoptotic properties [122,123].…”

Exploitation of Host Signaling Pathways by B Cell Superantigens—Potential Strategies for Developing Targeted Therapies in Systemic Autoimmunity

“…The protein tyrosine kinases (PTKs), Lck, Fyn, and ZAP‐70, were significantly decreased in T cells from HIV‐1‐positive subjects, and these alterations affected selectively T cells of HIV‐1‐infected patients since B cell PTKs, Syk and Lyn, were detected structurally and functionally intact 6 . Furthermore, CD45, a key positive phosphatase in multiple lymphocyte signaling pathways, is affected 8 . Impairment of CD45 activity correlates with disease progression and with levels of T cell apoptosis.…”

“…6 Furthermore, CD45, a key positive phosphatase in multiple lymphocyte signaling pathways, is affected. 8 Impairment of CD45 activity correlates with disease progression and with levels of T cell apoptosis. Altogether, these alterations may underlie the HIV-induced impairment of lymphocyte functions and may potentially predict disease progression.…”