HIV infection of primary CD4⁺ TH2 cells, defined by expression of the chemoattractant receptor-homologous (CRTH2), induces a Th0 phenotype

The association between HIV, cytokine profile, and disease progression is controversial. In this study, we evaluated whether HIV infection of a primary T helper-like type 2 cytokine (Th2) cell subset augments their cytokine profile. We utilized the CRTH2 (chemoattractant receptor-homologous) marker to identify CD4⁺Th2 cells. Approximately 2-4% of CD4⁺ T cells are CRTH2⁺. CRTH2⁺ expression is confirmed to delineate a Th2 subset as indicated by robust inducible IL-4 response. CD4⁺CRTH2 ⁺ T cells were also more inherently activated than their CRTH2-negative counterpart as indicated by a higher percent expression of CD69, CD45RO, CD95, CD25, and HLA-DR. CD4⁺CRTH2⁺ T cells were not terminally differentiated as indicated by expression of CD27 and CD28. In vitro HIV infection of primary human CD4⁺CRTH2⁺ T cells, independent of chemokine coreceptor usage, potently upregulated IFN-γ production while still maintaining robust IL-4 expression. This Th0 (IFNγ⁺IL-4⁺) phenotype was upregulated in CD4 ⁺CRTH2⁺ T cells post-HIV infection by 18-fold, demonstrating a shift to a Th0 phenotype. Ex vivo studies also demonstrated that HIV⁺ patients exhibited a decline in CD4⁺CRTH2 ⁺ cells and a shift of this population toward cells that express both IFN-γ and IL-4. Collectively, these data indicate that HIV replication in Th2 cells induces a Th0 phenotype. This phenomenon may be a deliberate viral escape mechanism to prevent the skewing of the immune response toward Th1 or Th2.