CD8+ T-Lymphocyte Response to Major Immunodominant Epitopes after Vaginal Exposure to Simian Immunodeficiency Virus: Too Late and Too Little
Matthew R. Reynolds,Eva G. Rakasz,Pamela J. Skinner,Cara White,Kristina Abel,Zhong-Min Ma,Lara Compton,Gnankang Napoé,Nancy A. Wilson,Christopher J. Miller,Ashley T. Haase,David I. Watkins +11 more
Reads0
Chats0
TLDR
The robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.Abstract:
In the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8+ T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletion of CD4+ T lymphocytes in gut-associated lymphatic tissue (GALT). We explored hypothetical explanations for this failure to clear infection and prevent CD4+ T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal transmission. We examined the relationship between the timing and magnitude of the CD8+ T-lymphocyte response to immunodominant SIV epitopes and viral replication, and we show first that the failure to contain infection is not because the female reproductive tract is a poor inductive site. We documented robust responses in cervicovaginal tissues and uterus, but only several days after the peak of virus production. Second, while we also documented a modest response in the draining genital and peripheral lymph nodes, the response at these sites also lagged behind peak virus production in these LT compartments. Third, we found that the response in GALT was surprisingly low or undetectable, possibly contributing to the severe and sustained depletion of CD4+ T lymphocytes in the GALT. Thus, the virus-specific CD8+ T-lymphocyte response is “too late and too little” to clear infection and prevent CD4+ T-lymphocyte loss. However, the robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.read more
Citations
More filters
Journal ArticleDOI
Targeting early infection to prevent HIV-1 mucosal transmission
TL;DR: Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.
Journal ArticleDOI
Perils at mucosal front lines for HIV and SIV and their hosts
TL;DR: This work has shown that HIV-1 and SIV risk elimination at the earliest stage of infection, at the mucosal point of entry, if founder populations of infected cells do not expand sufficiently to establish a self-propagating infection.
Journal ArticleDOI
Tissue-resident memory T cells
Haina Shin,Akiko Iwasaki +1 more
TL;DR: Different tissues in the body are categorized based on patterns of memory T‐cell migration and tissue residency, which describes the rules for TRM generation and the properties that distinguish them from circulating TEM and TCM cells.
Journal ArticleDOI
Early Events in Sexual Transmission of HIV and SIV and Opportunities for Interventions
TL;DR: A novel microbicide strategy that targets this innate response to prevent systemic infection and an agenda for future research that emphasizes mucosal immunology, virology and pathogenesis studies at each anatomic site of entry are concluded.
Journal ArticleDOI
Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1
Brandon F. Keele,Hui Li,Gerald H. Learn,Peter T. Hraber,Elena E. Giorgi,Elena E. Giorgi,Truman Grayson,Chuanxi Sun,Yalu Chen,Wendy W. Yeh,Norman L. Letvin,Norman L. Letvin,John R. Mascola,Gary J. Nabel,Barton F. Haynes,Tanmoy Bhattacharya,Tanmoy Bhattacharya,Alan S. Perelson,Bette T. Korber,Bette T. Korber,Beatrice H. Hahn,George M. Shaw +21 more
TL;DR: The molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques are determined to validate the SIV–macaque mucosal infection model for HIV-1 vaccine and microbicide research.
References
More filters
Journal ArticleDOI
Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.
Richard A. Koup,Jeffrey T. Safrit,Yunzhen Cao,C. A. Andrews,G. Mcleod,William Borkowsky,C. Farthing,David D. Ho +7 more
TL;DR: It is suggested that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and a role for CTL in protective immunity to HIV- 1 in vivo is indicated.
Journal ArticleDOI
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8+ Lymphocytes
Jörn E. Schmitz,Marcelo J. Kuroda,Sampa Santra,Vito G. Sasseville,Meredith A. Simon,Michelle A. Lifton,Paul Racz,Klara Tenner-Racz,Margaret Dalesandro,Bernhard J. Scallon,John Ghrayeb,Meryl A. Forman,David C. Montefiori,E. Peter Rieber,Norman L. Letvin,Keith A. Reimann +15 more
TL;DR: The results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.
Journal ArticleDOI
Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection.
TL;DR: HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.
Journal ArticleDOI
CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract
Jason M. Brenchley,Timothy W. Schacker,Laura E. Ruff,David Price,Jodie H. Taylor,Gregory J. Beilman,Phuong L. Nguyen,Alexander Khoruts,Matthew Larson,Ashley T. Haase,Daniel C. Douek +10 more
TL;DR: The nature and extent of CD4+ T cell depletion in lymphoid tissue is defined and mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4- T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation are pointed to.
Journal ArticleDOI
Gastrointestinal Tract as a Major Site of CD4+ T Cell Depletion and Viral Replication in SIV Infection
Ronald S. Veazey,Mary Ann DeMaria,Laura V. Chalifoux,Daniel E. Shvetz,Douglas R. Pauley,Heather Knight,Michael Rosenzweig,R. Paul Johnson,Ronald C. Desrosiers,Andrew A. Lackner +9 more
TL;DR: The intestine appears to be a major target for SIV replication and the major site of CD4+ T cell loss in early SIV infection.