Altered differentiation is central to HIV-specific CD4⁺ T cell dysfunction in progressive disease

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• The role of virus-specific CD4+ T cells in chronic infections like HIV is not well understood.
• Understanding CD4+ T cell dysfunction is crucial for developing effective HIV therapies.

Purpose of the Study:

• To investigate the transcriptional and functional characteristics of HIV-specific CD4+ T cells.
• To compare these cells in individuals with viremic infection, elite controllers, and those on antiretroviral therapy (ART).

Main Methods:

• Genome-wide transcriptional analyses of CD4+ T cells.
• Functional assays on T cells from HIV-infected individuals before and after ART initiation.
• Comparison with T cells from elite controllers.

Main Results:

• HIV-specific CD4+ T cells in viremic infection exhibit a T follicular helper (T_FH) cell-like profile.
• T cells from elite controllers show robust expression of T_H1, T_H17, and T_H22 genes.
• ART suppresses the T_FH-like profile but does not restore T_H1, T_H17, and T_H22 gene expression compared to elite controllers.

Conclusions:

• Altered differentiation, including both gain and loss of function, is central to HIV-specific CD4+ T cell impairment.
• ART impacts the T_FH profile but does not fully restore helper T cell subset function.