Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and...

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• CD4 T lymphocytes are crucial for immune function.
• HIV infection leads to a decline in CD4 T cells, impairing immunity.
• The specific CD4 T cell subsets targeted by HIV and the mechanisms of their depletion are not fully understood.

Purpose of the Study:

• To define the distinct CD4 T cell subsets sensitive or resistant to HIV-associated killing.
• To elucidate the mechanisms driving HIV-induced CD4 T cell depletion in lymphoid tissues.

Main Methods:

• Mass cytometry and single-cell RNA sequencing were employed on human tonsil lymphoid cells.
• Phenotypic and transcriptomic analyses were performed to characterize CD4 T cell subsets.

Main Results:

• HIV preferentially kills CD4 T cell subsets expressing CXCR5 and CXCR4.
• Preferentially infected subsets display an activated, exhausted effector memory phenotype.
• Preferentially killed cells show gene expression patterns associated with abortive HIV infection and pyroptosis.

Conclusions:

• HIV-induced CD4 T cell depletion involves a complex interplay with distinct tissue-based CD4 T cell subsets.
• Abortive infection and inflammatory programmed cell death (pyroptosis) significantly contribute to CD4 T cell loss in untreated HIV.
• Understanding these mechanisms is crucial for developing targeted therapeutic strategies against HIV.