Faculty Opinions recommendation of Central memory CD4+ T cell responses in chronic HIV infection are not restored by antiretroviral therapy.

ABSTRACT Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.

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HIV-Specific Cytolytic CD4 T Cell Responses During Acute HIV Infection Predict Disease Outcome

Science Translational Medicine ◽

10.1126/scitranslmed.3003165 ◽

2012 ◽

Vol 4 (123) ◽

pp. 123ra25-123ra25 ◽

Cited By ~ 153

Author(s):

D. Z. Soghoian ◽

H. Jessen ◽

M. Flanders ◽

K. Sierra-Davidson ◽

S. Cutler ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

T Cell Responses ◽

Cd4 T Cell ◽

Disease Outcome ◽

Acute Hiv Infection ◽

Cell Responses ◽

Acute Hiv

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Tetanus vaccination with IL-2 during highly active antiretroviral therapy induces sustained and pronounced specific CD4 T-cell responses

AIDS ◽

10.1097/00002030-200411050-00014 ◽

2004 ◽

Vol 18 (16) ◽

pp. 2199-2202 ◽

Cited By ~ 7

Author(s):

Gareth AD Hardy ◽

Nesrina Imami ◽

Ann K Sullivan ◽

Mark R Nelson ◽

Brian Gazzard ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses ◽

Highly Active ◽

Tetanus Vaccination

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Comparison of the Development of SARS-Coronavirus-2-Specific Cellular Immunity, and Central Memory CD4+ T-Cell Responses Following Infection versus Vaccination

Vaccines ◽

10.3390/vaccines9121439 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1439

Author(s):

Kevin M. Dennehy ◽

Eva Löll ◽

Christine Dhillon ◽

Johanna-Maria Classen ◽

Tobias D. Warm ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

T Cell Responses ◽

Central Memory ◽

Cd4 T Cell ◽

Memory T Cell ◽

Cell Responses ◽

Specific Effector ◽

Memory Cd4 T Cells

Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses—as measured by cytokine expression—and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells—indicative of the formation of the long-lived memory T-cell compartment—are comparably induced after infection and vaccination.

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Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus–Infected Women Despite Immune Reconstitution With Antiretroviral Therapy

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz678 ◽

2019 ◽

Vol 222 (2) ◽

pp. 243-251 ◽

Cited By ~ 2

Author(s):

Archana Thomas ◽

Erika Hammarlund ◽

Lina Gao ◽

Susan Holman ◽

Katherine G Michel ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Immune Reconstitution ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cd4 T Cell ◽

T Cell Memory ◽

Cell Memory ◽

Cell Responses ◽

Immunodeficiency Virus

Abstract Background It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections. Methods We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA). Results There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24–108 years; P = .001). Conclusions Despite antiretroviral therapy–associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.

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