TY - JOUR
T1 - HIV infection of primary CD4+ TH2 cells, defined by expression of the chemoattractant receptor-homologous (CRTH2), induces a Th0 phenotype
AU - Bahbouhi, Bouchaib
AU - Landay, Alan
AU - Tenorio, Allan
AU - Al-Harthi, Lena
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
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U2 - 10.1089/aid.2006.0151
DO - 10.1089/aid.2006.0151
M3 - Article
C2 - 17331033
AN - SCOPUS:33947201309
SN - 0889-2229
VL - 23
SP - 269
EP - 277
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 2
ER -