CD4 is a T lymphocyte receptor for major histocompatibility complex class II antigens. It is referred to as coreceptor because it synergizes with the T cell receptor for antigen when both receptors become engaged simultaneously. We show here in mice that when engaged by antibody independently of the T cell antigen receptor, CD4 induces T cells to undergo apoptosis. Several features of this process were identified. The expression of an intact Fas protein is a requirement for CD4-mediated T cell death. Mice homozygous for the lpr mutation which are defective in the expression of Fas and in their ability to delete lymphocytes apoptotically fail to delete anti-CD4-reactive T cells. Sessile anti-CD4-reactive T cells leave their homing environment in lymphoid organs and modulate their cell surface molecules, e.g. CD2, CD3, CD4. A massive influx of lymphoid cells with null-cell phenotype occurs in the blood where they begin to reexpress cell surface markers. With their arrival in the circulation, anti-CD4-reactive T cells develop features of DNA degradation typical of apoptosis. More than one third of the circulating lymphoid cells show apoptotic features 7-8 h after anti-CD4 injection. Their frequency declines subsequently presumably due to their physical disintegration via shedding of apoptotic bodies and phagocytosis. Our data show that when not obliged to the activation process by the antigen receptor, CD4 can mediate deletion signals. Thus, besides functioning as coreceptor with the antigen receptor, CD4 has a function of its own in facilitating the induction of apoptosis.

Proposed clinical indicators for efficient screening and testing for COVID-19 infection using Classification and Regression Trees (CART) analysis, Human Vaccines & Immunotherapeutics,

COVID-19 has had an unprecedented global impact on human health. Understanding the Ab memory responses to infection is one tool needed to effectively control the pandemic. Among 173 outpatients who had virologically confirmed SARS-CoV-2 infection, we evaluated serum Ab concentrations, microneutralization activity, and enumerated SARS-CoV-2–specific B cells in convalescent human blood specimens. Serum Ab concentrations were variable, allowing for stratification of the cohort into high and low responders. Neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein–specific B cells correlated with serum Ab concentration. Serum Ab concentration was positively associated with microneutralization activity and participant age, with participants under the age of 30 showing the lowest Ab level. These data suggest that young adult outpatients did not generate as robust Ab memory, compared with older adults. Body mass index was also positively correlated with serum Ab levels. Multivariate analyses showed that participant age and body mass index were independently associated with Ab levels. These findings have direct implications for public health policy and current vaccine efforts. Knowledge gained regarding Ab memory following infection will inform the need for vaccination in those previously infected and allow for a better approximation of population-wide protective immunity.

No abstract

Background Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. Methods Participants ages 4-21 were randomized to receive ccIIV4 (n =112) or LAIV4 (n=118). A novel high-throughput multiplex influenza antibody detection assay (MIADA) was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post vaccination. Results The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. Conclusions Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post vaccination response.