The helper (Th)2 cell-attracting
chemokines thymus and activation-regulated chemokine (TARC) and
macrophage-derived chemokine (MDC) are
ligands for the
chemokine receptor CCR4. A number of cellular sources of TARC and MDC have been identified, including not only macrophages, dendritic cells, and natural killer cells, but also bronchial epithelial cells. Recent studies report that TARC and MDC may serve as pivotal
chemokines for the development of Th2-dominated experimental
allergen-induced
asthma. This study was designed to assess TARC and MDC production by CD4+ T cells, including naive T cells and memory/effector T cells, purified from peripheral blood mononuclear cells in patients with
asthma. Asthmatic subjects included in this study had mild asthmatic symptoms, positive skin test responses to house dust mite
allergen, and elevated level of Dermatophagoides farinae
immunoglobulin E in the sera. CD4+ T cells--CD45RA+ CD4+ T cells--as naive T cells and CD45RO+ CD4+ T cells--as memory/effector T cells--were purified by negative selection from peripheral blood mononuclear cells obtained from asthmatic patients (n = 6) and healthy controls (n = 6). These cells and established Th1/Th2 cell lines were then cultured in the presence of both anti-CD3 and -CD28
antibodies. After 48 hr of incubation, concentrations of TARC, MDC,
interleukin (IL)-4,
IL-5, and
interferon-gamma in the supernatants were measured by
enzyme-linked
immunoadsorbent assay.
Reverse transcriptase-polymerase chain reaction was performed to analyze
mRNA expression of TARC and MDC. Our results clearly showed that TARC and MDC were produced by activated CD45RA+ CD4+ T cells rather than by activated CD45RO+ CD4+ T cells, and the levels of these
chemokines in the asthmatic patients were higher than those in the healthy controls. Furthermore, these
chemokines production by Th2 cell lines were greater than those by Th1 cell lines, but the level were smaller than those by naive T cells. Our studies suggest that TARC and MDC are produced by naive T cells rather than by memory/effector T cells, including Th2 cells, in asthmatic patients, and these
chemokines were produced at modest levels in any T-cell populations from healthy controls. Taken together, naive T cells in
asthma have a peculiar function to produce TRAC and MDC, which contribute to local migration of Th2 cells into lung and lymphoid tissues, along with a function as precursor for memory/effector T cell. This novel function of naive T cells may be implicated in the development of
asthma.