Functional dichotomy of CD4+ T helper lymphocytes in asymptomatic human immunodeficiency virus infection

✍ Scribed by Mario Clerici; Gene M. Shearer; Charles S. Via; Daniel R. Lucey; Emmanuel Roilides; Philip A. Pizzo

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 589 KB
• Volume: 21
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830210319

✦ Synopsis

Functional dichotomy of CD4+ T helper lymphocytes in asymptomatic human immunodeficiency virus infection

The majority of asymptomatic, human immune deficiency virus seropositive (HIV+) individuals exhibit a defect in CD4+ T helper cell (Th) function that is selective for responses to recall antigens, but not to HLA alloantigens. The CDCdependent Th response to HLA alloantigens (Allo) can be mediated by two distinct Th pathways: self-restricted CD4+ Th that recognize allogeneic determinants processed and presented by autologous or self accessory or antigenpresenting cells (SAC); and allo-restricted, CD4+ Th that recognize allogeneic determinants directly on allogeneic accessory or antigen-presenting cells (aAC). In contrast, the Th response to recall antigens requires CD4+ Th and SAC and is therefore limited to the major histocompatibility complex (h4HC) self-restricted pathway. Peripheral blood leukocytes from 56 asymptomatic HIV+ patients that exhibited a selective defect in CD4+ Th function were analyzed to determine whether the Th response to All0 was entirely functional, or whether one of the CDCmediated components of the A110 Th response was also defective. By depletion of AC and/or CD8+ Th subsets (to analyze CD4+ Th function), we demonstrated that HIV+ patients who were selectively deficient in Th function to recall antigens were also unresponsive to All0 presented by autologous AC (HLA self-restricted Th pathway), but retained AlloTh activity presented by allogeneic AC (allo-restricted CD4+ Th pathway).These findings indicate that the CD4+ Th defect seen in the majority of asymptomatic, HIV+ individuals is not limited to recall antigens, but also extends to the component of the response to HLA alloantigens that involves the self-restricted, CD4+ Th pathway. Thus, the Th defect observed in asymptomatic, HIV+ patients does not involve a CD4+ Th defect per se, but function.