Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate ...functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium.
Display omitted
•iCD8α cells are an innate lymphocyte population in the intestinal epithelium•iCD8α cells depend on IL-2Rγc, IL-15, and H2-T3 for development and maintenance•iCD8α cells are involved in early innate immune responses
Innate immune cells are critical for mucosal immunity. Olivares-Villagómez and colleagues report a population of CD8αα+ lymphocytes in the intestinal epithelium of mice and humans that possess innate-like features and contribute to mucosal immune responses.
A recent study reported that gene expression profiles from peripheral blood samples of healthy subjects prior to viral inoculation were indistinguishable from profiles of subjects who received viral ...challenge but remained asymptomatic and uninfected. If true, this implies that the host immune response does not have a molecular signature. Given the high sensitivity of microarray technology, we were intrigued by this result and hypothesize that it was an artifact of data analysis.
Using acute respiratory viral challenge microarray data, we developed a molecular signature that for the first time allowed for an accurate differentiation between uninfected subjects prior to viral inoculation and subjects who remained asymptomatic after the viral challenge.
Our findings suggest that molecular signatures can be used to characterize immune responses to viruses and may improve our understanding of susceptibility to viral infection with possible implications for vaccine development.
Somatic hypermutation of antibody genes is mediated by activation-induced cytidine deaminase and targets primarily hotspot motifs. We tested the hypothesis that the antibody variable genes of ...virus-specific B cells from infants exhibit a decreased frequency of somatic mutations compared with adults. We also sought to determine whether virus-specific B cells exhibit predominantly hotspot or randomly directed processes. We analyzed somatic mutations in rotavirus (RV)-specific B cells from otherwise healthy but recently RV-infected infants or adults in comparison with B cells from healthy volunteers not recently infected. We compared these antibody variable gene sequences with those derived from RV-specific B cells from an adult patient with X-linked hyper-IgM syndrome (XHIM). We found that the overall mutational frequency within the antibody variable region was lowest in RV-specific B cells from RV-infected infants, followed by randomly selected B cells, followed by RV-specific B cells from the patient with XHIM. RV-specific memory B cells from healthy adults exhibited the highest frequency of mutations. Approximately half of mutations in random or RV-specific B cells from adults or infants occurred at the DGYW/WRCH or WA/TW hotspot motifs. These findings suggest that virus-specific antibodies require both hotspot and randomly-directed processes.
Abstract
Fetal parvovirus B19 infection causes anemia, hydrops, and pregnancy loss but is generally not considered teratogenic. Nevertheless, disturbances of neuronal migration have been described ...with congenital parvovirus infection. We evaluated a term infant with congenital parvovirus disease and polymicrogyria. We compared this case with four other reports of central nervous system disease after birth to parvovirus-infected mothers. After an extensive diagnostic evaluation, this infant was found to have congenital parvovirus disease with severe anemia and nonimmune hydrops as well as extensive polymicrogyria. Although rare, this report and literature review suggest that parvovirus B19 has the potential to disrupt normal neurodevelopment. We suggest that infants with severe congenital parvovirus infection have close developmental surveillance and if symptomatic undergo neuroimaging to assess for disorders of neuromigration.
Antiviral antibody responses in infants are limited in quality. One reason for this finding could be that the majority of B cells in infants are CD5 super(+) cells, a subset of B cells that is ...thought to contain cells expressing polyreactive, low-affinity B cell receptors. We analyzed the rotavirus (RV)- specific antibody heavy chain variable region (VH) repertoire in CD5 super(+) and CD5 super(-) B cells of four RV-infected children between 10 and 19 months of age. We found that the RV-specific B cell repertoire in CD5 super(+) cells was VH3 family biased, in contrast to the VH1/VH4 dominance seen in CD5 super(-) B cells. The immunodominant RV-specific gene segment in CD5 super(-) B cells was VH1-46, which is the dominant segment used in RV-specific peripheral blood B cells from infants and adults. In contrast, the immunodominant gene segment was VH3-23 in RV- specific CD5 super(+) B cells, which is the dominant gene segment in randomly selected B cells. Both RV-specific CD5 super(+) and RV-specific CD5 super(-) B cells from all children studied demonstrated very low frequencies of somatic mutations. In conclusion, CD5 super(+) B cells in infants responding to RV use an antibody gene repertoire that differs from the virus-specific repertoire of CD5 super(-) B cells, and both CD5 super(+) and CD5 super(-) RV-specific B cells exhibit a low frequency of somatic mutations.
Memory B cells expressing the intestinal homing marker alpha sub(4) beta sub(7) are important for protective immunity against human rotavirus (RV). It is not known whether the B cell repertoire of ...intestinal homing B cells differs from B cells of the systemic compartment. In this study, we analyzed the RV-specific V sub(H) and V sub(L) repertoire in human IgD super(-) B cells expressing the intestinal homing marker alpha sub(4) beta sub(7). The mean frequency of RV-specific B cells in the systemic compartment of healthy adult subjects was 0.6% (range, 0.2-1.2). The mean frequency of IgD super(-) B cells that were both RV specific and alpha sub(4) beta sub(7) was 0.04% (range, 0.01-0.1), and a mean of 10% (range, 1-32) of RV-specific peripheral blood human B cells exhibited an intestinal homing phenotype. We previously demonstrated that VH1-46 is the dominant Ab H chain gene segment in RV-specific systemic B cells from adults and infants. RV-specific systemic IgD super(-) or intestinal homing IgD super(-)/ alpha sub(4) beta sub(7) super(+) B cells in the current study also used the gene segment VH1-46 at a high frequency, while randomly selected B cells with those phenotypes did not. These data show that VH1-46 is the immunodominant gene segment in human RV-specific effector B cells in both the systemic compartment and in intestinal homing lymphocytes. The mean replacement/silent mutation ratio of systemic compartment IgD super(-) B cells was >2, consistent with a memory phenotype and antigenic selection. Interestingly, RV-specific intestinal homing IgD super(-)/ alpha sub(4) beta sub(7) super(+) B cells using the VH1-46 gene segment were not mutated, in contrast to systemic RV-specific IgD super(-) B cells.
Erythematous plaques and papules on a premature infant Riemenschneider, Kelsie, BS; Redenius, Rachel, MD; Reese, Jeff, MD ...
Journal of the American Academy of Dermatology,
2016, Volume:
76, Issue:
4
Journal Article
PDF
