Naïve CD4 T cells can differentiate into multiple functionally-defined memory CD4 T cell subsets. The types of memory CD4 T cells which exist in tissues of HIV/SIV-infected individuals are perturbed compared to healthy individuals. The mechanisms underlying these functional perturbations remain unclear. Here we assess whether viral infection of functionally-defined memory CD4 T cells might contribute, and how these populations of memory CD4 T cells contribute to, the total pool of infected CD4 T cells and plasma viremia.
Lymphocytes from Peripheral Blood Mononuclear Cells (PBMC), spleen, and Mesenteric Lymph Nodes (MLN) of SIV+ rhesus macaques were isolated and simulated for 6 hours with PMA and ionomycin in the presence of Brefeldin A. CD28+ memory CD4 T cells were studied and CCR6+/IL-17+ and IL-17- CD4 T cells (Th17 cells), CCR4-/IFNg+ and IFNg- CD4 T cells (Th1 cells), CCR4+/IFNg-/IL-17- CD4 T cells (Th2 cells) and FoxP3+ CD4 T cells (Tregs) were then flow cytometrically isolated, and the proportions of cells harboring SIV DNA were then assessed through qPCR.
Viral DNA was detected in all subsets of memory CD4 T cells (irrespective of functionality, phenotype, or anatomic location). However, irrespective of anatomic site studied, we found that no one population of isolated memory, CD28+, CD4 T cells harbored more (or less) viral DNA than any other population of memory CD4 T cells.
Loss of CD4 T cells is a hallmark of progressive HIV/SIV infection and several studies have shown that Th17 cells are preferentially loss from mucosal tissues and lymph nodes that drain mucosal tissues. However, our data suggest that preferential infection of Th17 cells is unlikely to cause this immunological perturbation. Moreover, we see a positive correlation between the size of a T helper subset population and its contribution to the infected memory pool. Thus, functional differentiation of memory CD4 T cells is unlikely to influence their susceptibility to infection in vivo.