To address this issue, a series of mechanisms are proposed, supported by evidence from different fields, by which CD38 overexpression can facilitate CD4 T cell depletion in HIV infection.
As efficient humoral immune responses are important in controlling HIV-disease progression, we characterized the memory B cell population for its subsets and their activation (CD38 expression) and functional [interleukin (IL)-21R expression] profile in individuals with nonprogressive [long-term nonprogressors (LTNPs), <i>N</i> = 16] and progressive HIV disease (progressors, <i>N</i> = 16) along with 10 HIV uninfected healthy controls (HCs).
Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection.
After LcS ingestion, peripheral CD4⁺ T-cell and Th2 (CXCR3<sup>-</sup>CCR6<sup>-</sup>CD4⁺) counts significantly increased in both HIV-infected groups; Th17 (CXCR3<sup>-</sup>CCR6⁺CD4⁺) counts increased in all three groups; regulatory T-cell (CD25<sup>high</sup>CD4⁺) counts decreased in the ART(+) and HIV(-) groups; activated CD8⁺ cells (CD38⁺HLA-DR⁺CD8⁺) decreased from 27.5% to 13.2% (<i>p</i> < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but significantly among HIV(+) children.
Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38(+) HLA-DR(+) T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8(+) T-cell compartment.
CD38 is a powerful disease marker for human leukemias and myelomas, is directly involved in the pathogenesis and outcome of human immunodeficiency virus infection and chronic lymphocytic leukemia, and controls insulin release and the development of diabetes.
We compared the number/percentages of naive and memory CD4+ T-cells, CD38+ CD8+ T-cells, and CD28+ CD4+ and CD28+ CD8+ T-cells in patients with advanced HIV disease (baseline CD4+ count < 100) with those with less advanced (baseline CD4+ cell count > 100) HIV disease during 4 years of suppressive highly active antiretroviral therapy.
During HIV infection, CD4+ CD38+ T-cells are the predominant circulating CD4+ subset whose HLA-DR positivity increases with disease progression and whose V beta repertoire is similar to that of CD4+ CD38- T-cells.