Double-negative T cells during HIV/SIV infections

Abstract

Purpose of the review This review summarizes the role of CD3+CD4−CD8− double-negative T cells, which have both regulatory and helper T cell function and may have the potential to compensate for the reduced levels of CD4+ T cells during SIV/HIV infection. Recent findings Double-negative (DN) T cells have been characterized in several human diseases and in murine models of autoimmunity and transplantation, where they exhibit both immunoregulatory and helper T cell-like function. During the natural nonpathogenic SIV infection of African nonhuman primates, the lack of clinical disease progression is associated with the presence of DN T cells that maintain helper T cell functions while remaining refractory to viral infection. Moreover, DN T cells may compensate for very low levels of CD4+ T cells observed in a cohort of sooty mangabeys that have been infected with SIV for over 10 years and have remained free of clinical disease manifestations associated with AIDS. These studies identify a potential for DN T cells to provide critical helper function during HIV infection. Summary DN T cells with some CD4+ T cell functions are associated with a nonpathogenic outcome during SIV infection and represent a potential immune therapeutic target in HIV-infected patients.

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

“…Compared to blood (40,41), our data shows CD3 + CD4 -CD8 -DN T cells are the dominant CD3 + cells in macaques' tonsils for the first time. Other studies have suggested that DN T participates in inflammatory diseases and viral infections, including HIV (42,43). Contrary to these other studies, we found a significant loss of DN T in the tonsils during chronic SIV infection.…”

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

“…Compared to blood (40,41), our data shows CD3 + CD4 -CD8 -DN T cells are the dominant CD3 + cells in macaques' tonsils for the first time. Other studies have suggested that DN T participates in inflammatory diseases and viral infections, including HIV (42,43). Contrary to these other studies, we found a significant loss of DN T in the tonsils during chronic SIV infection.…”

Double‐negative T cells: Setting the stage for disease control or progression

“…In patients with primary HIV infection, these facts together predicted the onset of immune activation, marked by an increase in CD8 + lymphocytes [105]. In agreement, Sundaravaradan, studying DN T cells in HIV+ patients, concluded that these cells exhibit an immunoregulatory and auxiliary profile, similar to CD4+ T cells, which seems to contribute to halting the progression of the infection [106]. The data from these studies show that regulatory DN T cells would be important to compensate for reduced levels of CD4+ T cells during HIV infection, thereby controlling an exaggerated and harmful immune response.…”

Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15] Transforming growth factor-beta 1 and interleukin-10-producing DNT cells are associated with the control of chronic immune activation, which plays an essential role in the pathogenesis of HIV infection and is a key predictor of progression to AIDS. [9,10] Furthermore, DNT cells seem to be involved in the immune reconstitution occurring during ART and to predict future immune activation.…”

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15]…”

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

“…Compared to blood (40,41), our data shows CD3 + CD4 -CD8 -DN T cells are the dominant CD3 + cells in macaques' tonsils for the first time. Other studies have suggested that DN T participates in inflammatory diseases and viral infections, including HIV (42,43). Contrary to these other studies, we found a significant loss of DN T in the tonsils during chronic SIV infection.…”

Double‐negative T cells: Setting the stage for disease control or progression

“…In patients with primary HIV infection, these facts together predicted the onset of immune activation, marked by an increase in CD8 + lymphocytes [105]. In agreement, Sundaravaradan, studying DN T cells in HIV+ patients, concluded that these cells exhibit an immunoregulatory and auxiliary profile, similar to CD4+ T cells, which seems to contribute to halting the progression of the infection [106]. The data from these studies show that regulatory DN T cells would be important to compensate for reduced levels of CD4+ T cells during HIV infection, thereby controlling an exaggerated and harmful immune response.…”

Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15] Transforming growth factor-beta 1 and interleukin-10-producing DNT cells are associated with the control of chronic immune activation, which plays an essential role in the pathogenesis of HIV infection and is a key predictor of progression to AIDS. [9,10] Furthermore, DNT cells seem to be involved in the immune reconstitution occurring during ART and to predict future immune activation.…”

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15]…”

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

“…Compared to blood (40,41), our data shows CD3 + CD4 -CD8 -DN T cells are the dominant CD3 + cells in macaques' tonsils for the first time. Other studies have suggested that DN T participates in inflammatory diseases and viral infections, including HIV (42,43). Contrary to these other studies, we found a significant loss of DN T in the tonsils during chronic SIV infection.…”

Double‐negative T cells: Setting the stage for disease control or progression

“…In patients with primary HIV infection, these facts together predicted the onset of immune activation, marked by an increase in CD8 + lymphocytes [105]. In agreement, Sundaravaradan, studying DN T cells in HIV+ patients, concluded that these cells exhibit an immunoregulatory and auxiliary profile, similar to CD4+ T cells, which seems to contribute to halting the progression of the infection [106]. The data from these studies show that regulatory DN T cells would be important to compensate for reduced levels of CD4+ T cells during HIV infection, thereby controlling an exaggerated and harmful immune response.…”

Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15] Transforming growth factor-beta 1 and interleukin-10-producing DNT cells are associated with the control of chronic immune activation, which plays an essential role in the pathogenesis of HIV infection and is a key predictor of progression to AIDS. [9,10] Furthermore, DNT cells seem to be involved in the immune reconstitution occurring during ART and to predict future immune activation.…”

“…[16,17] These primates exhibit up to 40% of DNT cells that are capable of proliferating and producing T helper cytokines following antigen stimulation. [6,15]…”