Vigorous HIV-1-Specific CD4 ⁺ T Cell Responses Associated with Control of Viremia

Abstract

Virus-specific CD4+ T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus-type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4+ T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta chemokines. In persons with chronic infection, HIV-1-specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1-specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1-specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development.

Infection dynamics in HIV-specific CD4 T cells: Does a CD4 T cell boost benefit the host or the virus?

“…The model is based on previous work which investigated virus spread via the mitotic division of T cells [9,10] and is given by the following set of differential equations. (2) The dynamics may converge to two different stable equilibria. (i) The CD4 T cell response, and thus virus replication in specific T cells, does not become established.…”

“…(The higher the virus load, the more efficient the rate of mitotic spread). Infection of HIV-specific CD4 T cells can also result in efficient impairment of effector responses, such as cytotoxic T lymphocytes (CTL) or antibodies, because the ability to deliver help may be subverted [2][3][4].…”

Maintenance of memory CTL responses by T helper cells and CD40‐CD40 ligand: antibodies provide the key

“…This may be extrapolated to other viruses causing persistent infections, in particular HIV. For HIV, it has been shown that long-term control of viral replication is tightly associated with the maintenance of a functional Th cell response [43][44][45]. Moreover, induction of HIV-specific neutralizing antibodies shows kinetics that are comparable to those observed after LCMV infection [46].…”

Apoptosis of HIV-specific CD8+ T cells: an HIV evasion strategy

“…113 On the contrary, control of viremia was associated with a polyclonal, vigorous HIVspecific CD4 þ T-cell response accompanied by a strong CTL response. 114 As mentioned, reconstitution of CD28 expression in CD28 HIV-specific CD8 þ T cells results in the restoration of autocrine production of IL-2 and antigen-specific proliferation, suggesting an increased dependence on CD4 þ T-cell help in the absence of CD28 and impaired ability for IL-2 production. 105 Furthermore, diminished IL-2 could further deteriorate the CTL response through the downregulation of proliferation of HIV-specific CD4 þ T cells.…”