engleski

Depletion of CCR4+ and CXCR3+ T lymphocytes from peripheral blood in acute RSV infection

Undeveloped immune system in infants is considered to be responsible for the severe RSV infections in infants (i.e. bronchiolitis) since virus can skew antiviral type-1 to less effective type-2 immune reaction. Accumulation of lymphocytes in the lungs, during RSV infection, is mediated by type-1 chemokines (IP-10, MIG and fractalkine) through binding of CXCR3 and CX3CR1. Opposing type-2 chemokines (TARC and MDC) are responsible for migration of CCR4-positive lymphocytes involved in allergic immune responses. We postulate that RSV- infected infants produce elevated type-2 chemokines and compromise antiviral response. PBMC from RSV-, adenovirus/influenza-infected infants and RSV-infants collected 4-6 weeks after first sampling were simultaneously stained with antibodies for chemokine receptors (CCR4, CXCR3, CX3CR1) and lymphocyte subpopulation markers. Serum chemokines (TARC, MDC, IP-10, MIG, fractalkline) were determined by ELISA. CD4+ T- lymphocytes bearing CCR4 and CXCR3 were depleted from peripheral blood in RSV-infected infants, compared to infants with adenovirus/influenza infections. Interestingly, more B-lymphocytes of RSV-infected infants express CCR4, CXCR3 and CX3CR1 compared to adenovirus/influenza-infected infants. In convalescent phase, percentages of CCR4+ and CXCR3+ CD4+ T-lymphocytes increased while percentages of CCR4+, CXCR3+ and CX3CR1+ B- cells decreased. In acute phase of RSV infections, the predominant chemokines were TARC, MDC and IP- 10. In convalescent phase serum levels of TARC, MDC and IP-10 decreased. In conclusion, we observed a mixed type of chemokine production and chemokine receptors level during acute phase of RSV infection. Higher TARC levels and CCR4 positive lymphocytes could contribute to type-2 cytokine synthesis and confront effective type-1 cytokine-driven antiviral immune response.

RSV; chemokine; infants; IP-10; MIG; fractalkine; TARC; MDC

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