HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cell responses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decrease in viraemia

Abstract

HAART for 6 months restored antigen-specific CD4 T-cell response to several antigens. In vitro immune reconstitution was closely correlated with an increase in memory CD4 cells. Restoration of delayed type hypersensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia following HAART may allow an improved inflammatory reaction, thus providing even stronger immune reconstitution.

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

“…In adults the restoration of CD4 + T-lymphocyte responses in vitro is more frequent to antigens of high exposure pathogens (C. albicans) than to those of low exposure antigens (tetanus toxoid) [17]. In contrast, in the population of children enrolled in this study, the frequency of restoration of the T-lymphocyte response was the same for both antigens (seven of seven cases).…”

“…However, the restoration of antigen-specific T-lymphocyte responses was closely related with an increase in CD4 + T-lymphocyte numbers [17] and was associated (in the majority of cases) with a suppression of viral load.…”

“…It has been reported that HAART induces an improvement in CD4 + T-lymphocyte reactivity for clinically relevant pathogens [3,4,17]. However, the restoration of antigen-specific T-lymphocyte responses was closely related with an increase in CD4 + T-lymphocyte numbers [17] and was associated (in the majority of cases) with a suppression of viral load.…”

“…The in vitro T-lymphocyte response is restored in adults [17] and children [18] Baseline 3·51 4·11 2·92 5·11 4·9 4·8 4·58 1 month 3·14 3·2 2·94 4·28 3·35 4·9 2 3 months 2·95 4·05 2·27 4·33 2·94 5·08 3·21 6 months 2·69 4·64 2·27 4·8 4·03 4·96 4·3 12 months 2·95 3·61 2·54 4·3 4·3 5·31 3·9 CD4 + cells/ml (%) Baseline 468 (29) 816 (42) 450 (15) 342 (17) (11) 400 (16) 164 (7) 333 (17) 451 (11) 259 (20) lymphocyte counts despite incomplete virus suppression or even virological failure [19][20][21][22][23]. In a recent study Chougnet et al [24] observed that in a group of HIV-1 infected children treated with HAART for >2 years there was a marked increase in the proliferative response and skin reactivity to recall antigen.…”

Relative Resistance in the Development of T Cell Anergy in CD4+ T Cells from Simian Immunodeficiency Virus Disease-Resistant Sooty Mangabeys

“…Although indirect, these data suggest that the remaining CD4 ϩ T cells are likely to be CD45RO ϩ (unless an unusual subset replaces the potentially depleted CD45RO ϩ T cells) and that differences in anergy induction are not likely due to frequency issues but due to function. Second, the initiation of highly active antiretroviral therapy has been shown to lead not only to the expansion of existing memory cells (50,51), but also to the gradual restoration of both Ag-specific and anti-CD3-elicited memory T cell proliferative responses to immune stimuli (52)(53)(54) suggesting that the Ag specific memory cells are present in such patients but are "unresponsive" or "anergic." Further support for this view emanates from the finding that the interruption of highly active antiretroviral therapy in HIV-infected patients rekindles such anergy and leads to the rapid decrease of T cell responses (55).…”