T Cells From Individuals in Advanced Stages of HIV-1 Infection Do Not Proliferate but Express Activation Antigens in Response to HIV-1-Specific Antigens

Abstract

Like T cells from healthy subjects, those of HIV-1-infected patients are capable of expressing activation antigens on their surface after antigenic or mitogenic stimulation, but their proliferative activity is strongly reduced or even absent, especially in patients with advanced stages of the disease. The characteristic of expressing activation antigens in response to different stimuli in the absence of cell proliferation is shared by CD4+ and CD8+ T-cell subsets from HIV-1-infected patients. The number of T cells capable of expressing CD25 and CD71 in response to HIV-1-related antigens but not of proliferating increased significantly with the progression of the disease, but the number of T cells capable of expressing the two activation antigens in response to the classic tetanus toxoid recall antigen decreased. The higher numbers of T cells capable of responding to HIV-1-related antigens in conjunction with a reduction in the number of T cells responding to recall antigens may explain the occurrence of different infections, including opportunistic microorganisms, during the more advanced stages of HIV-1 infection. Because the increase in the number of HIV-1 antigen-responding T cells (defined by CD25 and CD71 activation antigen expression) is a characteristic of symptomatic HIV-1-infected patients, expression (by flow cytometry) of these activation antigens on T cells in response to HIV-1 antigens could be used as a new marker of disease progression.

Expression of CD69 on T-cells from HIV-1-infected children and adolescents increases with increasing viral load

“…Recently, similar results were obtained in a cohort of HIV-1 infected intravenous drug abusers in advanced stages of the disease [7]. PHA-stimulated T-cells from these patients showed expression levels of the activation antigens CD25 and CD71 that were similar to those seen in healthy adult controls; however, in contrast to the controls, T-cells from patients showed a reduced proliferation rate in vitro.…”

Abnormal intracellular IL-2 and interferon-gamma (IFN-γ) production as HIV-1-associated markers of immune dysfunction

“…On the other hand, our results show a significant decrease in the proportion of CD4 þ T cells producing IL-2 in HIV þ symptomatics versus asymptomatics, and an inverse correlation between percentage IL-2 þ CD4 þ T cells and RNA viral load, suggesting that the defect in IL-2 production is progressive. It would therefore be interesting to investigate the mitogen-induced production of IL-2 from proliferating and nonproliferating CD4 þ T cells using flow cytometry, since this may have relevance to the impaired antigen-specific immune responses in activated T helper cells from HIV-infected patients [20]. A number of non-cytopathic viruses encode proteins which can interfere with anti-viral host immunity and thus modulate the immune response in favour of maintaining a chronic viral persistence in the host [21].…”

In Vitro p24 Antigen-Stimulated Lymphocyte Proliferation and β-Chemokine Production in Human Immunodeficiency Virus Type 1 (HIV-1)-Seropositive Subjects after Immunization with an Inactivated gp120-Depleted HIV-1 Immunogen (Remune)

“…In contrast, subjects were able to mount responses against cytomegalovirus, herpes simplex virus, and PHA. Defects in HIV-1specific lymphocyte proliferative responses prior to the loss of recall, allogeneic, and mitogen antigen responses in HIV-1infected individuals have now been described in numerous clinical studies (2,5,14,16). Recently, it has been shown that HIV-1-specific lymphocytes responses to p24 antigen could be augmented in subjects on antiviral therapy prior to seroconversion (16).…”