CD45 isoform expression is associated with different susceptibilities of human naive and effector CD4⁺ T cells to respond to IL‐4

Abstract

Interleukin-4 (IL-4) is the major factor promoting the development of T helper type 2 (Th2) cells from naive precursor T cells. Minute amounts of IL-4 produced by naive T cells seem to be sufficient; however, the molecular mechanisms explaining this efficient utilization of are not yet known. Here, we show that human CD4 + CD45RA + naive T cells, in contrast to CD4 + CD45R0 + effector T cells, show responsiveness to endogenous as well as exogenous IL-4 to proliferate and differentiate towards Th2 cells in vitro. Despite production levels of IL-4 below conventional detection limits, CD45RA + T cell-derived IL-4 could clearly activate STAT6. Although the expression levels of IL-4R and STAT6 were not different between naive and effector T cells, only naive T cells responded to IL-4 in a STAT6-dependent reporter gene assay. Transfecting a trans-dominant negative form of STAT6 abrogated IL-4-induced proliferation in CD45RA + cells. A significantly higher protein tyrosine phosphatase (PTPase) activity was detected in CD45R0 + T cells as compared to CD45RA + T cells. Cross-linking CD45 potently reduced PTPase activity in CD45R0 + T cells and restored their ability to proliferate in response to IL-4. Thus, CD45 PTPase activity contributes to the susceptibility of naive and memory T cells to respond to IL-4.

Immune cellular parameters of leprosy and human immunodeficiency virus‐1 co‐infected subjects

“…These responses may be influenced by the genetic background of the individual as well as by environmental factors 44 . We suggest that the continuing production of IL‐4 by HIV‐1 and M. leprae ‐specific T cells may create a ‘Th2 environment’ in which the priming of T cells to heterologous antigens is biased towards IL‐4 production 45 . Exploring the association of higher IL‐4 production after PMA and ionomycin stimulation, and expansion of T EM , may present an opportunity to elucidate the mechanisms involved in the possibly deleterious effect of M. leprae infection in HIV‐1‐infected patients observed in our study.…”

“…Demographic, clinical, microbiological and laboratory characteristics are detailed in Table 1. The median ages of all participants was 38 years (IQR: [35][36][37][38][39][40][41][42][43][44][45][46][47][48]) and most were male (83Á9%). No difference in gender distribution was observed between groups.…”

Antioxidants as Novel Agents for Asthma

“…These genes include cytokines (e.g., IL-4, IL-5, IL-8, IL-9, IL-15, and TNF-α), chemokines (e.g., RANTES, eotaxin, and monocyte chemotactic protein-3), and adhesion molecules (e.g., ICAM-1 and VCAM-1) (Fig. 4) [51][52][53]. In our recent study, we have assessed whether these genes are up-regulated by oxidative stress in the OVA-induced asthma model.…”

Seasonal dynamics of chemokine receptors and CD62L in subjects with asymptomatic skin sensitization to birch and grass pollen

“…T helper 2 (Th 2 ) cells arise from the pool of naïve precursor T cells as a result of activation with antigen (allergen) presenting cells (APC). As fully differentiated cells, Th 2 cells express CD45R0, the short isoform of the CD45 phosphotyrosine phosphatase, associated with the memory phenotype (3). CD45R0 may, because of transient expression, be viewed as a marker for recent T‐cell activation (4).…”