Reduced Numbers of T-Cell, B-Cell, and CD4+ Follicular Helper T Cell (Tfh) Populations in Infants With Acute Respiratory Syncytial Virus (RSV) Infection

Abstract

Background. Our previous studies suggest that relative peripheral blood lymphopenia is associated with worse clinical outcomes in previously healthy children with acute RSV infection. Whether the lymphopenia is driven by a decreased in the T or B cell numbers has not been well characterized. We sought to characterize the T, including Tfh, and B cellular immune responses induced by RSV infection in previously healthy children representative of the whole disease spectrum. Methods. Previously healthy infants with RSV infection were enrolled and blood samples obtained at the time of evaluation in the emergency department (outpatients) or within 24 hours of hospitalization (inpatients). Healthy age-matched controls (HC) were also enrolled. Using the differences in T cell, B cell and CD4+ Tfh cell numbers and subsets according to disease severity defined as the need for hospitalization. Results. We enrolled a total of 64 children: 21 RSV+ outpatients, 11 RSV+ inpatients and 32 healthy age-matched controls. Overall, inpatients were younger than outpatients (median age: 2.2 versus 7.9 months; p < 0.001). Total absolute numbers of CD3 + , CD8+ and effector CD8+ T cells were reduced in both RSV+ inpatients and outpatients compared with HC (p < 0.01), while total CD4+ and naive CD4+ T-cells were decreased only in outpatients (p < 0.01). On the other hand, absolute CD19+ B cell numbers and subsets were not significantly different between RSV groups, except for plasma B cells which were lower in inpatients versus outpatients (p = 0.03). Lastly, Tfh2 (CXCR3- CCR6), but not Tfh1 (CXCR3 + CCR6-) or Th17 (CCR6 + CXCR3-), were decreased only in patients hospitalized with RSV infection but not in outpatients (p = 0.027). Conclusion. RSV infection was associated with reduced absolute numbers of total CD8+ T and CD8+ effector cells independent of disease severity, while the overall numbers of B-cells were minimally affected. Further studies are needed to understand the long-term impact of this dysfunctional immune response.