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

ABSTRACTAttrition within the CD4+T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8+T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8+T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38+CD27−CD8+T cells characterized by the low expression of the CD8 receptor (CD8dim). Interestingly, while high frequencies of HIV-specific CD8+T cell responses occur within the CD38+CD27−CD8dimT cell population, the minority populations of CD8brightT cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dimT cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8dimT cells, and the size of this population inversely correlates with the acute loss of CD4+T cells. These data indicate, for the first time, that early CD4+T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8dimT cell population less efficient in controlling HIV viremia.IMPORTANCEA distinct population of activated CD8+T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8+T cell dysfunction during acute infection.

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

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020334.233434 ◽

2004 ◽

Author(s):

Luis J Montaner

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

T Cell Responses ◽

Central Memory ◽

Cd4 T Cell ◽

Cell Responses ◽

Chronic Hiv Infection

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TRAILshort Protects against CD4 T Cell Death during Acute HIV Infection

The Journal of Immunology ◽

10.4049/jimmunol.1900271 ◽

2019 ◽

Vol 203 (3) ◽

pp. 718-724

Author(s):

Sekar Natesampillai ◽

Ana C. Paim ◽

Nathan W. Cummins ◽

Aswath P. Chandrasekar ◽

Gary D. Bren ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Hiv Infection ◽

Cd4 T Cell ◽

Acute Hiv Infection ◽

Acute Hiv

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HIV-specific cytolytic CD4 T-cell responses effectively control HIV infection in macrophages

Retrovirology ◽

10.1186/1742-4690-9-s2-p274 ◽

2012 ◽

Vol 9 (S2) ◽

Author(s):

DZ Soghoian ◽

M Flanders ◽

K Sierra-Davidson ◽

S Ranasinghe ◽

S Cutler ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses

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897. Trends and Correlation of HIV-1 Reservoir in Acute HIV Infection and Chronic HIV Infection in China

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1092 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S539-S540

Author(s):

Shuang peng ◽

Ming wang

Keyword(s):

T Cell ◽

Hiv Infection ◽

Mean Value ◽

Cd4 T Cell ◽

Acute Hiv Infection ◽

Cell Percentage ◽

Acute Hiv ◽

The Mean ◽

Hiv 1 ◽

Chronic Hiv Infection

Abstract Background Among acute HIV infection （AHI）and chronic HIV infection（CHI）,the association of HIV-1 DNA and HIV-1 RNA is currently a hot spot of concern. We studied HIV-1 DNA levels in patients with AHI and CHI before initiation of ART to explore the growth characteristics of the HIV reservoir. Methods From 2016/10/31 to 2020/11/23, 97 patients were enrolled in the first hospital of Changsha in China. According to the patient’s epidemiological history, HIV-1 antibody conversion time, presence of opportunistic infection（OI）, to determine whether the patients were in the acute or chronic infection period, and divided into two arms: AHI and CHI. Lleukomonocyte, HIV-1 RNA, and CD4/8 of all patients were collected. The HIV-1 DNA in peripheral blood mononuclear (PBMC) was detected by PCR-Fluorescence Probing. The results were analyzed by SPSS 22.0 and GraphPad Prism 8.0. P-value < 0.05 were statistically significant. Results 93 of 97 were male and 85 of 97 with sexual transmission. In AHI arm, the mean of HIV-1 RNA was 5.15 log10 copies/ml, and the mean of HIV-1 DNA was 2.83 log10 copies/106 PBMCs. In CHI Arm, the mean value of HIV-1 RNA was 4.90 log10 copies/ml, and the mean value of HIV-1 DNA was 3.19 log copies/106 PBMCs. The HIV-1 DNA of CHI group was higher than that of AHI group (p = 0.002) , but the HIV-1 RNA of CHI group was lower than that of AHI Group (p = 0.183) . There were no significant differences between AHI and CHI in age, sex, body weight, route of infection, ART, other viral infection, leukomonocyte, CD4+ T cell count, CD4+ T cell percentage, CD8+ T cell count, CD8+ T cell percentage and CD4/CD8 ratio (P > 0.05).In Group AHI, HIV-1 DNA was positively correlated with HIV-1 RNA (r = 0.548, p < 0.001), but not in Group CHI (r = 0.14, p = 0.347). Conclusion Patients with AHI have lower HIV-1 DNA levels and smaller viral reservoir than those with CHI. These data have illustrates the benefits of rapid treatment. The correlation between HIV-1 DNA and HIV-1 RNA in patients with acute infection is strong,the level of HIV-1 DNA increased with the increase of HIV-1 RNA level, but was not related to CD4 + T cells, CD8 + T cells and CD4/CD8 ratio. Disclosures All Authors: No reported disclosures

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Central Memory CD4+T Cell Responses in Chronic HIV Infection Are Not Restored by Antiretroviral Therapy

The Journal of Immunology ◽

10.4049/jimmunol.173.3.2184 ◽

2004 ◽

Vol 173 (3) ◽

pp. 2184-2189 ◽

Cited By ~ 54

Author(s):

Mohamed Elrefaei ◽

Michael D. McElroy ◽

Christopher P. Preas ◽

Rebecca Hoh ◽

Steven Deeks ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

T Cell Responses ◽

Central Memory ◽

Cd4 T Cell ◽

Cell Responses ◽

Chronic Hiv Infection

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CD4 T-Cell Responses in Primary HIV Infection: Interrelationship with Immune Activation and Virus Burden

Frontiers in Immunology ◽

10.3389/fimmu.2016.00395 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 7

Author(s):

Mathieu F. Chevalier ◽

Céline Didier ◽

Pierre-Marie Girard ◽

Maria E. Manea ◽

Pauline Campa ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Immune Activation ◽

T Cell Responses ◽

Cd4 T Cell ◽

Primary Hiv Infection ◽

Cell Responses

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Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in Components of HIV Vaccine Regimens in Humans

Journal of Virology ◽

10.1128/jvi.01143-18 ◽

2018 ◽

Vol 92 (23) ◽

Cited By ~ 5

Author(s):

Franco Pissani ◽

Bianca Schulte ◽

Michael A. Eller ◽

Bruce T. Schultz ◽

Silvia Ratto-Kim ◽

...

Keyword(s):

Clinical Trials ◽

T Cells ◽

T Cell ◽

Immune Responses ◽

Hiv Infection ◽

Cd4 T Cells ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses ◽

Hiv 1

ABSTRACT To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; P = 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-α)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion. IMPORTANCE Only one HIV-1 candidate vaccine strategy has shown protection, albeit marginally (31%), against HIV-1 acquisition, and correlates of protection suggested that a multifunctional CD4 T cell immune response may be important for this protective effect. Therefore, the functional phenotypes of HIV-specific CD4 T cell responses induced by different phase I and phase II clinical trials were assessed to better show how different vaccine strategies influence the phenotype and function of HIV-specific CD4 T cell immune responses. The significance of this research lies in our comprehensive comparison of the compositions of the T cell immune responses to different HIV vaccine modalities. Specifically, our work allows for the evaluation of vaccination strategies in terms of their success at inducing Tfh cell populations.

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