Abstract
Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8+ cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log10 RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8+ T cells and significant CD8+ T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4+ T cells characterized as CD45RA-CD28 +CD95+CCR7- and also granzyme B+, suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4+ T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8+ T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3348-3358 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 185 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 15 2010 |
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ASJC Scopus subject areas
- Immunology
Cite this
Emergence of simian immunodeficiency virus-specific cytotoxic CD4 + T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus. / Von Gegerfelt, Agneta; Valentin, Antonio; Alicea, Candido; Van Rompay, Koen K.A.; Marthas, Marta; Montefiori, David C.; Pavlakis, George N.; Felber, Barbara K.
In: Journal of Immunology, Vol. 185, No. 6, 15.09.2010, p. 3348-3358.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Emergence of simian immunodeficiency virus-specific cytotoxic CD4 + T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus
AU - Von Gegerfelt, Agneta
AU - Valentin, Antonio
AU - Alicea, Candido
AU - Van Rompay, Koen K.A.
AU - Marthas, Marta
AU - Montefiori, David C.
AU - Pavlakis, George N.
AU - Felber, Barbara K.
PY - 2010/9/15
Y1 - 2010/9/15
N2 - Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8+ cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log10 RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8+ T cells and significant CD8+ T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4+ T cells characterized as CD45RA-CD28 +CD95+CCR7- and also granzyme B+, suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4+ T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8+ T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.
AB - Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8+ cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log10 RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8+ T cells and significant CD8+ T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4+ T cells characterized as CD45RA-CD28 +CD95+CCR7- and also granzyme B+, suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4+ T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8+ T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.
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U2 - 10.4049/jimmunol.1000572
DO - 10.4049/jimmunol.1000572
M3 - Article
VL - 185
SP - 3348
EP - 3358
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -